Ignite Creation Date:
2025-12-25 @ 3:28 AM
Ignite Modification Date:
2025-12-26 @ 2:09 AM
Study NCT ID:
NCT06727305
Status:
RECRUITING
Last Update Posted:
2025-09-30
First Post:
2024-11-20
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
MTOR Inhibitors in Older Adults
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D013607', 'term': 'Tablets'}, {'id': 'D000068338', 'term': 'Everolimus'}], 'ancestors': [{'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D004304', 'term': 'Dosage Forms'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Patients who will be randomized in 1:1:1:1:1:1 ratios to receive oral tablet doses of sirolimus and everolimus with concentrations of 0.5mg, 1mg, 2mg each'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 60}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-11', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2027-11-13', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-24', 'studyFirstSubmitDate': '2024-11-20', 'studyFirstSubmitQcDate': '2024-12-08', 'lastUpdatePostDateStruct': {'date': '2025-09-30', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2024-12-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-09-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Cmax for Sirolimus', 'timeFrame': 'Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose', 'description': 'Maximum Sirolimus Concentration at Steady State (Cmax)'}, {'measure': 'Cmax for Everolimus', 'timeFrame': 'Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose', 'description': 'Maximum Everolimus Concentration at Steady State (Cmax)'}, {'measure': 'Ctrough for Sirolimus', 'timeFrame': 'Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose', 'description': 'Trough Sirolimus Concentration at Steady State (Ctrough)'}, {'measure': 'Ctrough for Everolimus', 'timeFrame': 'Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose', 'description': 'Trough Everolimus Concentration at Steady State (Ctrough)'}, {'measure': 'AUC for Sirolimus', 'timeFrame': 'Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose', 'description': 'Sirolimus Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) at Steady State'}, {'measure': 'AUC for Everolimus', 'timeFrame': 'Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose', 'description': 'Everolimus Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) at Steady State'}, {'measure': 'CL/F for Sirolimus', 'timeFrame': 'Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose', 'description': 'Sirolimus Apparent Oral Clearance (CL/F)'}, {'measure': 'CL/F for for Everolimus', 'timeFrame': 'Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose', 'description': 'Everolimus Apparent Oral Clearance (CL/F)'}, {'measure': 'S6K Activity, in Sirolimus cohorts', 'timeFrame': 'Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose on Day 1 and Day 14', 'description': 'Pharmacodynamic parameter, S6K Activity, in Sirolimus cohorts'}, {'measure': 'S6K Activity, in Everolimus cohorts', 'timeFrame': 'Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2.5, 3, 4, 6, and 12-hour post dose on Day 1 and Day 14', 'description': 'Pharmacodynamic parameter, S6K Activity, in Everolimus cohorts'}, {'measure': 'Senescence-associated secretory phenotype (SASP) index', 'timeFrame': 'Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13', 'description': 'Clinical biomarker parameter (SASP) index is a clinical biomarker parameter that measures the level of proteins secreted by senescent cells in the body.'}, {'measure': 'Erythrocyte sedimentation rate (ESR)', 'timeFrame': 'Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13', 'description': 'Clinical biomarker parameter (ESR) is a blood test that detects and monitors inflammation in the body.'}, {'measure': 'C-reactive protein (CRP)', 'timeFrame': 'Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13', 'description': 'A measure of Clinical biomarker parameter (CRP), is an inflammatory marker.'}, {'measure': '6-minute walk test (6MWT)', 'timeFrame': 'Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13', 'description': 'The 6MWT is simply a record of the distance (in meters) traveled by a given patient at his or her self-selected walking speed over a period of six minutes.'}, {'measure': 'Short physical performance battery (SPPB)', 'timeFrame': 'Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13', 'description': 'Clinical biomarker parameter (SPPB) assesses lower extremity function in older adults. The test battery consists of three physical tasks (walking, sit-to-stand and balance) to assess functional mobility. The test will be performed according to standardized procedure. The maximal total score is 12 and higher total scores indicate a better lower extremity functioning.'}], 'secondaryOutcomes': [{'measure': 'Change in SASP response at 3 months follow-up', 'timeFrame': 'Baseline, 3 months', 'description': 'SASP (senescence-associated secretory phenotype) index score is quantified using blood work comparing results at baseline and at 3 months follow-up. Patients with high SASP scores have a poor survival rate, while patients with low SASP scores have a good survival rate.'}, {'measure': 'Change in Laboratory Biomarker response (ESR) from baseline at 3 months follow-up', 'timeFrame': 'Baseline, 3 months', 'description': 'Feasibility of collecting the laboratory biomarker - Erythrocyte sedimentation rate (ESR) is assessed by change in blood work readings ((millimeters per hour \\[mm/hour\\])) at 3 months follow-up.'}, {'measure': 'Change in laboratory Biomarker response (CRP) from baseline at 3 months follow-up', 'timeFrame': 'Baseline, 3 months', 'description': 'Feasibility of collecting the laboratory biomarker- C-Reactive Protein (CRP) is assessed by change in blood work readings (mg/dl) at 3 months follow-up.'}, {'measure': 'Change in laboratory Biomarker response (S6K activity) from baseline at 3 months follow-up', 'timeFrame': 'Baseline, 3 months', 'description': 'Feasibility of collecting the laboratory biomarker- S6 Kinase (S6K) activity is assessed by change in blood work readings (mg/dl) at 3 months follow-up.'}, {'measure': 'Change in laboratory Biomarker response (mitochondrial function) from baseline at 3 months follow-up', 'timeFrame': 'Baseline, 3 months', 'description': 'Feasibility of collecting the laboratory biomarker (mitochondrial function) is assessed by change in blood work readings at 3 months follow-up. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.'}, {'measure': 'Change in laboratory Biomarker response (metabolomics) from baseline at 3 months follow-up', 'timeFrame': 'Baseline, 3 months', 'description': 'Feasibility of collecting the laboratory biomarker (metabolomics) is assessed by change in blood work readings at 3 months follow-up. Changes in blood metabolomics are quantified by measuring the concentration levels of individual metabolites within a blood sample using techniques like mass spectrometry (MS) or nuclear magnetic resonance (NMR) spectroscopy, where the relative abundance of each metabolite is compared between different samples, allowing for identification of changes in metabolic pathways based on variations in metabolite levels. The unit of measure is "concentration", usually expressed in micromolar (µM) or millimolar (mM), as it represents the quantity of a specific metabolite per unit volume of the sample.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Aging', 'Geriatic', 'Disability'], 'conditions': ['Aging']}, 'descriptionModule': {'briefSummary': 'Over the past decades, healthcare systems face significant challenges to meet the needs of an aging population due to progressive debility, functional decline and chronic diseases development. While there is a growing appreciation of the potential impact of mTOR inhibitors on slowing aging processes, preventing chronic disease and prolonging healthy lifespan, a major challenge in developing clinical trials to establish the clinical efficacy of mTOR inhibitors is the absence of pharmacokinetics (PK) and pharmacodynamics (PD) data in older adults. The proposed study will provide the foundation for future clinical trials assessing the role of mTOR inhibitors on aging related indications', 'detailedDescription': 'Study Objectives To characterize Pharmacokinetics (PK) and Pharmacodynamics (PD) of mTOR Inhibitors and determine whether mTOR Inhibitors will improve phenotypic biomarkers of aging as measured by SASP (senescence-associated secretory phenotype) index score at 3 months follow-up in older adults.\n\nSpecific Aims:\n\nAim 1: To characterize Pharmacokinetics (PK) and Pharmacodynamics (PD) of mTOR Inhibitors (sirolimus and everolimus) in older adults.\n\nAim 2: To determine whether mTOR Inhibitors will improve phenotypic biomarkers of aging as measured by SASP (senescence-associated secretory phenotype) index score at 3 months follow-up.\n\nExploratory Aim 3: We will also assess the feasibility of collecting the laboratory biomarkers (ESR, CRP, S6K activity, mitochondrial function, metabolomics) and data regarding the functional biomarkers of aging measured by walking speed, chair stand, standing balance, grip strength'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '65 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Community-dwelling adults\n2. Patients should be 65 Years and older\n3. Patients is able to understand and follow trial procedures\n\nExclusion Criteria:\n\n1. Creatinine clearance \\<30 mL/min;\n2. History of chronic liver disease;\n3. Uncontrolled Hypertension (i.e., systolic blood pressure \\>160 mm Hg);\n4. Hemorrhagic central nervous system (CNS) event within 1 year from screening visit;\n5. Thrombotic event (DVT,PE) within 1 year from screening visit if not on anticoagulation;\n6. Planned major surgical procedures;\n7. Cardiovascular diseases ( i.e., admission for heart failure or myocardial infarction within 12 months);\n8. Taking medication that increase or decrease sirolimus blood concentrations;\n9. Other investigational therapy received within 1 month prior to screening visit;\n10. History of dementia; 11 Dependence in any Katz Basic Activities of Daily Living.'}, 'identificationModule': {'nctId': 'NCT06727305', 'briefTitle': 'MTOR Inhibitors in Older Adults', 'organization': {'class': 'OTHER', 'fullName': 'University of Texas Southwestern Medical Center'}, 'officialTitle': 'Characterization of mTOR Inhibitor Pharmacokinetics and Pharmacodynamics in Older Adults .', 'orgStudyIdInfo': {'id': 'STU-2024-0798'}, 'secondaryIdInfos': [{'id': '1U01AG081450-01A1', 'link': 'https://reporter.nih.gov/quickSearch/1U01AG081450-01A1', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'sirolimus 0.5 mg Arm', 'description': 'Participant would receive 0.5 mg of sirolimus.', 'interventionNames': ['Drug: Sirolimus 0.5 Mg Oral Tablet']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'sirolimus 1 mg Arm', 'description': 'Participant would receive 1 mg of sirolimus.', 'interventionNames': ['Drug: Sirolimus 1Mg Oral Tablet']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'sirolimus 2 mg Arm', 'description': 'Participant would receive 2 mg of sirolimus.', 'interventionNames': ['Drug: Sirolimus 2 MG Oral Tablet']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'everolimus 0.5 mg Arm', 'description': 'Participant would receive 0.5 mg of Everolimus.', 'interventionNames': ['Drug: Everolimus 0.5 MG Oral Tablet']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'everolimus 1 mg Arm', 'description': 'Participant would receive 1 mg of Everolimus.', 'interventionNames': ['Drug: Everolimus 1 MG Oral Tablet']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'everolimus 2 mg Arm', 'description': 'Participant would receive 2 mg of Everolimus.', 'interventionNames': ['Drug: Everolimus 2 MG Oral Tablet']}], 'interventions': [{'name': 'Sirolimus 0.5 Mg Oral Tablet', 'type': 'DRUG', 'description': 'Sirolimus 0.5 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.', 'armGroupLabels': ['sirolimus 0.5 mg Arm']}, {'name': 'Sirolimus 1Mg Oral Tablet', 'type': 'DRUG', 'description': 'Sirolimus 1 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.', 'armGroupLabels': ['sirolimus 1 mg Arm']}, {'name': 'Sirolimus 2 MG Oral Tablet', 'type': 'DRUG', 'description': 'Sirolimus 2 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.', 'armGroupLabels': ['sirolimus 2 mg Arm']}, {'name': 'Everolimus 0.5 MG Oral Tablet', 'type': 'DRUG', 'description': 'Everolimus 0.5 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.', 'armGroupLabels': ['everolimus 0.5 mg Arm']}, {'name': 'Everolimus 1 MG Oral Tablet', 'type': 'DRUG', 'description': 'Everolimus 1 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.', 'armGroupLabels': ['everolimus 1 mg Arm']}, {'name': 'Everolimus 2 MG Oral Tablet', 'type': 'DRUG', 'description': 'Everolimus 2 mg oral tablets for daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.', 'armGroupLabels': ['everolimus 2 mg Arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75390', 'city': 'Dallas', 'state': 'Texas', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Rhoda Annoh Gordon, PharmD, MPH', 'role': 'CONTACT', 'email': 'Rhoda.annohgordon@utsouthwestern.edu', 'phone': '2146457108'}], 'facility': 'UT Southwestern Medical Center', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}], 'centralContacts': [{'name': 'Irina Timofte, MD, MS', 'role': 'CONTACT', 'email': 'Irina.Timofte@utsouthwestern.edu', 'phone': '2163347534'}], 'overallOfficials': [{'name': 'Irina Timofte, MD, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Texas Southwestern Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Texas Southwestern Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Maryland, Baltimore', 'class': 'OTHER'}, {'name': 'National Institute on Aging (NIA)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'Irina Timofte', 'investigatorAffiliation': 'University of Texas Southwestern Medical Center'}}}}