Ignite Creation Date:
2025-12-24 @ 7:44 PM
Ignite Modification Date:
2025-12-25 @ 5:22 PM
Study NCT ID:
NCT03461003
Status:
COMPLETED
Last Update Posted:
2022-09-09
First Post:
2018-01-31
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
N-of-1 Trials In Children With Hypertension
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2021-11-22', 'type': 'ACTUAL'}}}}, 'interventionBrowseModule': {'meshes': [{'id': 'D017311', 'term': 'Amlodipine'}, {'id': 'D017706', 'term': 'Lisinopril'}, {'id': 'D006852', 'term': 'Hydrochlorothiazide'}, {'id': 'D019808', 'term': 'Losartan'}], 'ancestors': [{'id': 'D004095', 'term': 'Dihydropyridines'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D004151', 'term': 'Dipeptides'}, {'id': 'D009842', 'term': 'Oligopeptides'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D002740', 'term': 'Chlorothiazide'}, {'id': 'D001581', 'term': 'Benzothiadiazines'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D049971', 'term': 'Thiazides'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D001713', 'term': 'Biphenyl Compounds'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D013777', 'term': 'Tetrazoles'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'joyce.samuel@uth.tmc.edu', 'phone': '713-500-6708', 'title': 'Joyce P Samuel, MD, MS', 'organization': 'The University of Texas Health Science Center at Houston'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '6 months', 'eventGroups': [{'id': 'EG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive', 'otherNumAtRisk': 23, 'deathsNumAtRisk': 23, 'otherNumAffected': 0, 'seriousNumAtRisk': 23, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 3, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 26, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Tiredness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 26, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Sleeping Poorly', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 26, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'OG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}], 'classes': [{'categories': [{'title': 'Controlled', 'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}, {'title': 'Uncontrolled', 'measurements': [{'value': '10', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '6 months from enrollment', 'description': "Blood pressure control is when ambulatory blood pressure is normal, with normal as defined by the American Heart Association (AHA) criteria \\[the AHA criteria are systolic blood pressure and diastolic blood pressure (throughout wake and sleep) less than the 95th percentile based on the patient's gender and height\\]. To assess ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period.", 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Mean 24-hour Ambulatory Systolic Blood Pressure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'OG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}], 'classes': [{'categories': [{'measurements': [{'value': '-10.6', 'spread': '9.301', 'groupId': 'OG000'}, {'value': '-5.1', 'spread': '9.586', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline, 6 months', 'description': 'To assess 24-hour mean ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period, while awake and while asleep. The mean of all recordings over the 24-hour period is calculated per participant for both baseline and 6 months, and then the mean 24-hour systolic blood pressure at 6 months minus the mean 24-hour systolic blood pressure at baseline is calculated per participant. The average difference is reported, with a negative value indicating a reduction in blood pressure over time.', 'unitOfMeasure': 'mmHg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'One patient in each arm was missing a baseline ambulatory blood pressure monitoring (ABPM), so change from baseline could not be calculated for each of those participants'}, {'type': 'SECONDARY', 'title': 'Change in Mean Wake Ambulatory Systolic Blood Pressure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'OG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}], 'classes': [{'categories': [{'measurements': [{'value': '-10.5', 'spread': '7.747', 'groupId': 'OG000'}, {'value': '-6.2', 'spread': '10.123', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline, 6 months', 'description': 'To assess mean wake ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24 hour period, throughout wake and sleep. The mean of all recordings that occur while the participant is awake during the 24-hour period is calculated for both baseline and 6 months, and then the mean wake systolic blood pressure at 6 months minus the mean wake systolic blood pressure at baseline is calculated per participant. The average difference is reported, with a negative value indicating a reduction in blood pressure over time.', 'unitOfMeasure': 'mmHg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'One patient in each arm was missing a baseline ambulatory blood pressure monitoring (ABPM), so change from baseline could not be calculated for each of those participants'}, {'type': 'SECONDARY', 'title': 'Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'OG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'from baseline to 6 months', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Data were not collected from 5 participants in the NICHE method arm, and data were not collected from 5 participants in the Usual Care arm'}, {'type': 'SECONDARY', 'title': 'Number of Participants Who Self-reported Adherence to Intervention', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'OG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}], 'classes': [{'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'from month 5 to month 6', 'description': 'Adherence is reported as the number of participants who self-reported at the 6-month visit that they had not missed any doses of their medication in the preceding month.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Data were not collected for 3 participants in the NICHE method arm.'}, {'type': 'SECONDARY', 'title': 'Patient Satisfaction With Intervention as Assessed by a Survey', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'OG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}], 'classes': [{'categories': [{'measurements': [{'value': '9.929', 'spread': '0.267', 'groupId': 'OG000'}, {'value': '9.667', 'spread': '0.730', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6 months', 'description': 'Patient satisfaction is scored from 0 to 10, where 0 is the worst health care possible and 10 is the best health care possible.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Data were not collected for 4 participants in the NICHE method arm. Data were not collected for 2 participants in the Usual Care arm.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'FG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '23'}, {'groupId': 'FG001', 'numSubjects': '26'}]}, {'type': 'Received Intervention', 'achievements': [{'groupId': 'FG000', 'numSubjects': '21'}, {'groupId': 'FG001', 'numSubjects': '22'}]}, {'type': 'Completed 6-month Follow up', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'groupId': 'FG001', 'numSubjects': '23'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'groupId': 'FG001', 'numSubjects': '23'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'NICHE Method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.\n\nNICHE method: Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.\n\nAmlodipine: Calcium-channel blocker; antihypertensive\n\nLisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive\n\nHydrochlorothiazide: Thiazide diuretic; antihypertensive\n\nLosartan: Angiotensin II receptor blocker (ARB); antihypertensive'}, {'id': 'BG001', 'title': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.\n\nUsual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '15.9', 'groupId': 'BG000', 'lowerLimit': '14.7', 'upperLimit': '16.9'}, {'value': '15.9', 'groupId': 'BG001', 'lowerLimit': '14.4', 'upperLimit': '16.8'}, {'value': '15.9', 'groupId': 'BG002', 'lowerLimit': '14.7', 'upperLimit': '16.9'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '16', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '33', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Hispanic (black or white)', 'measurements': [{'value': '17', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '35', 'groupId': 'BG002'}]}, {'title': 'White (non-Hispanic)', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Black (non-Hispanic)', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Other', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Primary language of parent', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'title': 'English', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}]}, {'title': 'Spanish', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Clinic Site', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Multidisciplinary HTN clinic', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}, {'title': 'County based clinic', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '23', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Hypertension type', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Primary', 'measurements': [{'value': '17', 'groupId': 'BG000'}, {'value': '22', 'groupId': 'BG001'}, {'value': '39', 'groupId': 'BG002'}]}, {'title': 'Secondary', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Mean 24-hour ambulatory blood pressure at baseline (without medication)', 'classes': [{'title': 'Systolic blood pressure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '24', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '130', 'groupId': 'BG000', 'lowerLimit': '126', 'upperLimit': '133'}, {'value': '130', 'groupId': 'BG001', 'lowerLimit': '127', 'upperLimit': '134'}, {'value': '130', 'groupId': 'BG002', 'lowerLimit': '127', 'upperLimit': '134'}]}]}, {'title': 'Diastolic blood pressure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '24', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '76', 'groupId': 'BG000', 'lowerLimit': '71', 'upperLimit': '80'}, {'value': '76', 'groupId': 'BG001', 'lowerLimit': '74', 'upperLimit': '81'}, {'value': '76', 'groupId': 'BG002', 'lowerLimit': '71', 'upperLimit': '81'}]}]}], 'paramType': 'MEDIAN', 'description': 'To assess 24-hour ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period, while awake and while asleep. The mean of all recordings over the 24-hour period is calculated per participant, and the median of these means is reported.', 'unitOfMeasure': 'mm Hg', 'dispersionType': 'INTER_QUARTILE_RANGE', 'populationDescription': 'Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm'}, {'title': 'BMI percentile for gender and age', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '96.8', 'groupId': 'BG000', 'lowerLimit': '10.5', 'upperLimit': '99.8'}, {'value': '95.8', 'groupId': 'BG001', 'lowerLimit': '49.0', 'upperLimit': '99.8'}, {'value': '96', 'groupId': 'BG002', 'lowerLimit': '10.5', 'upperLimit': '99.8'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'percentile', 'dispersionType': 'FULL_RANGE'}, {'title': 'BMI categories', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Underweight', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Health weight', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}, {'title': 'Overweight', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}]}, {'title': 'Obese', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Number of participants with Chronic Kidney Disease', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Number of participants with Diabetes Mellitus', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Number of participants with Proteinuria', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Number of participants who avoid calcium channel blocker', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-09-26', 'size': 1175063, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_002.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2021-10-01T15:22', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 49}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-04-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-08', 'completionDateStruct': {'date': '2021-05-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-08-16', 'studyFirstSubmitDate': '2018-01-31', 'resultsFirstSubmitDate': '2021-10-21', 'studyFirstSubmitQcDate': '2018-03-07', 'lastUpdatePostDateStruct': {'date': '2022-09-09', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2022-08-16', 'studyFirstPostDateStruct': {'date': '2018-03-09', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2022-09-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-11-14', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months', 'timeFrame': '6 months from enrollment', 'description': "Blood pressure control is when ambulatory blood pressure is normal, with normal as defined by the American Heart Association (AHA) criteria \\[the AHA criteria are systolic blood pressure and diastolic blood pressure (throughout wake and sleep) less than the 95th percentile based on the patient's gender and height\\]. To assess ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period."}], 'secondaryOutcomes': [{'measure': 'Change in Mean 24-hour Ambulatory Systolic Blood Pressure', 'timeFrame': 'baseline, 6 months', 'description': 'To assess 24-hour mean ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period, while awake and while asleep. The mean of all recordings over the 24-hour period is calculated per participant for both baseline and 6 months, and then the mean 24-hour systolic blood pressure at 6 months minus the mean 24-hour systolic blood pressure at baseline is calculated per participant. The average difference is reported, with a negative value indicating a reduction in blood pressure over time.'}, {'measure': 'Change in Mean Wake Ambulatory Systolic Blood Pressure', 'timeFrame': 'baseline, 6 months', 'description': 'To assess mean wake ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24 hour period, throughout wake and sleep. The mean of all recordings that occur while the participant is awake during the 24-hour period is calculated for both baseline and 6 months, and then the mean wake systolic blood pressure at 6 months minus the mean wake systolic blood pressure at baseline is calculated per participant. The average difference is reported, with a negative value indicating a reduction in blood pressure over time.'}, {'measure': 'Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication', 'timeFrame': 'from baseline to 6 months'}, {'measure': 'Number of Participants Who Self-reported Adherence to Intervention', 'timeFrame': 'from month 5 to month 6', 'description': 'Adherence is reported as the number of participants who self-reported at the 6-month visit that they had not missed any doses of their medication in the preceding month.'}, {'measure': 'Patient Satisfaction With Intervention as Assessed by a Survey', 'timeFrame': '6 months', 'description': 'Patient satisfaction is scored from 0 to 10, where 0 is the worst health care possible and 10 is the best health care possible.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Pediatric Hypertension']}, 'referencesModule': {'references': [{'pmid': '24591341', 'type': 'BACKGROUND', 'citation': 'Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, Zachariah JP, Urbina EM; American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension. 2014 May;63(5):1116-35. doi: 10.1161/HYP.0000000000000007. Epub 2014 Mar 3. No abstract available.'}, {'pmid': '36227203', 'type': 'DERIVED', 'citation': 'Samuel JP, Bell CS, Samuels JA, Rajan C, Walton AK, Green C, Tyson JE. N-of-1 Trials vs. Usual Care in Children With Hypertension: A Pilot Randomized Clinical Trial. Am J Hypertens. 2023 Feb 13;36(2):126-132. doi: 10.1093/ajh/hpac117.'}]}, 'descriptionModule': {'briefSummary': "The single patient (n-of-1) randomized trial is an underused approach to resolving therapeutic uncertainty by using a patient's own data to inform an individualized treatment plan. The proposed research is designed to assess whether the n-of-1 trial approach improves blood pressure control compared to usual care. This trial aims to advance learning about not only the treatment of pediatric hypertension but also the use of a neglected type of randomized trial to optimize the care of each patient.", 'detailedDescription': 'Pediatric hypertension, a growing problem, often requires prescription of antihypertensive medication. Pediatric hypertension specialists lack an evidentiary base on which to establish definitive clinical practice guidelines for first-line therapy. Significant practice variation is an unsurprising consequence. Routine choice of the same first-line therapy for most patients with hypertension, absent testing other options, may delay correction of blood pressure for months or years. Failure to incorporate patient preferences in medical decision-making may also contribute to decreased patient satisfaction and adherence.\n\nLarge parallel-group, comparative effectiveness trials are likely not on the horizon for this population. Moreover, heterogeneity of treatment effects would minimize the generalizability of such a trial to all patients.\n\nThis is a parallel-group, randomized clinical trial to compare the n-of-1 trial approach to usual care in normalizing blood pressure while minimizing exposure to compliance-reducing side effects.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '22 Years', 'minimumAge': '10 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* treating physician determines that pharmacologic therapy is indicated for treatment of hypertension\n* ambulatory hypertension has been confirmed (off meds) within 12 months of enrollment\n\nExclusion Criteria:\n\n* age \\< 10 years\n* resistant hypertension (requiring ≥ 3 drug therapy)\n* absolute contraindication or allergy to any of the tested drugs.'}, 'identificationModule': {'nctId': 'NCT03461003', 'acronym': 'NICHE', 'briefTitle': 'N-of-1 Trials In Children With Hypertension', 'organization': {'class': 'OTHER', 'fullName': 'The University of Texas Health Science Center, Houston'}, 'officialTitle': 'A Randomized Clinical Trial of the N-of-1 Approach in Children With Hypertension', 'orgStudyIdInfo': {'id': 'HSC-MS-17-1014'}, 'secondaryIdInfos': [{'id': 'UL1TR003167', 'link': 'https://reporter.nih.gov/quickSearch/UL1TR003167', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'NICHE method', 'description': 'In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.', 'interventionNames': ['Other: NICHE method', 'Drug: Amlodipine', 'Drug: Lisinopril', 'Drug: Hydrochlorothiazide', 'Drug: Losartan']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Usual Care', 'description': 'No protocol will be introduced to standardize BP management in the control arm.', 'interventionNames': ['Other: Usual care']}], 'interventions': [{'name': 'NICHE method', 'type': 'OTHER', 'description': 'Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.', 'armGroupLabels': ['NICHE method']}, {'name': 'Usual care', 'type': 'OTHER', 'description': 'Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.', 'armGroupLabels': ['Usual Care']}, {'name': 'Amlodipine', 'type': 'DRUG', 'description': 'Calcium-channel blocker; antihypertensive', 'armGroupLabels': ['NICHE method']}, {'name': 'Lisinopril', 'type': 'DRUG', 'description': 'Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive', 'armGroupLabels': ['NICHE method']}, {'name': 'Hydrochlorothiazide', 'type': 'DRUG', 'description': 'Thiazide diuretic; antihypertensive', 'armGroupLabels': ['NICHE method']}, {'name': 'Losartan', 'type': 'DRUG', 'description': 'Angiotensin II receptor blocker (ARB); antihypertensive', 'armGroupLabels': ['NICHE method']}]}, 'contactsLocationsModule': {'locations': [{'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas Health Science Center at Houston', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}], 'overallOfficials': [{'name': 'Joyce P. Samuel, MD, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The University of Texas Health Science Center, Houston'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The University of Texas Health Science Center, Houston', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Center for Advancing Translational Sciences (NCATS)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor of Pediatrics', 'investigatorFullName': 'Joyce Philip Samuel', 'investigatorAffiliation': 'The University of Texas Health Science Center, Houston'}}}}