Ignite Creation Date:
2025-12-25 @ 3:18 AM
Ignite Modification Date:
2025-12-26 @ 1:56 AM
Study NCT ID:
NCT05598905
Status:
COMPLETED
Last Update Posted:
2024-06-04
First Post:
2022-10-13
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Combined Effect of Pregabalin and Oxycodone, and Lacosamide and Oxycodone, on Breathing
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069583', 'term': 'Pregabalin'}, {'id': 'D010098', 'term': 'Oxycodone'}, {'id': 'D000078334', 'term': 'Lacosamide'}], 'ancestors': [{'id': 'D005680', 'term': 'gamma-Aminobutyric Acid'}, {'id': 'D000613', 'term': 'Aminobutyrates'}, {'id': 'D002087', 'term': 'Butyrates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D003061', 'term': 'Codeine'}, {'id': 'D009022', 'term': 'Morphine Derivatives'}, {'id': 'D009019', 'term': 'Morphinans'}, {'id': 'D053610', 'term': 'Opiate Alkaloids'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}, {'id': 'D006576', 'term': 'Heterocyclic Compounds, 4 or More Rings'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D010616', 'term': 'Phenanthrenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D000081', 'term': 'Acetamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D000085', 'term': 'Acetates'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2024-01-17', 'size': 347511, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_000.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2024-06-03T05:04', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR'], 'maskingDescription': 'Double-blind cross-over trial in which the order of visits is randomized.\n\nAmendment:\n\nIn order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone as a visit 3 was added.'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Double-blind, randomized cross-over design.\n\nAmendment:\n\nIn order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone as a visit 3 was added.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-10-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-06', 'completionDateStruct': {'date': '2024-01-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-06-03', 'studyFirstSubmitDate': '2022-10-13', 'studyFirstSubmitQcDate': '2022-10-27', 'lastUpdatePostDateStruct': {'date': '2024-06-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-10-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-01-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Ventilation', 'timeFrame': 'Study day 1', 'description': 'The primary endpoint of the study is the change in ventilation at an increased level of CO2'}, {'measure': 'Ventilation', 'timeFrame': 'Study day 2', 'description': 'The primary endpoint of the study is the change in ventilation at an increased level of CO2'}], 'secondaryOutcomes': [{'measure': 'Level of sedation', 'timeFrame': 'Study day 1', 'description': 'The subjects will be queried using Visual Analogue Scales from 0-10 cm (range from no effect to most severe effect), every hour after dosing up to 8h'}, {'measure': 'Pain relief', 'timeFrame': 'Study day 1', 'description': 'The relief of pain is measured using a painful stimulus (eg pressure pain)'}, {'measure': 'Occurence of nausea/vomiting', 'timeFrame': 'Study day 1', 'description': 'The subjects will be queried using Visual Analogue Scales from 0-10 cm (range from no effect to most severe effect).'}, {'measure': 'pupil diameter', 'timeFrame': 'Study day 1', 'description': 'Measurement of pupil diameter following drug intake.'}, {'measure': 'Baseline ventilation', 'timeFrame': 'Study day 1', 'description': 'Minute ventilation in L/min prior to increasing inhaled CO2.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Oxycodone', 'Pregabalin', 'Lacosamide'], 'conditions': ['Opioid-induced Respiratory Depression']}, 'descriptionModule': {'briefSummary': 'Opioids are commonly prescribed for moderate to severe pain. While initially intended for moderate to severe acute and cancer pain, opioids are currently frequently considered and prescribed in chronic noncancer pain. Due to the large increase in opioid prescription rate, the number of unintentional drug overdoses is rapidly increasing, not only in the Unites States but also in the Netherlands. A potential lethal consequence of an opioid overdose is opioid-induced respiratory depression. Additionally, it is well known that opioids are often used (and abused) in combination with other legal or illicit substances, for example alcohol, benzodiazepines, cannabis, neuropathic pain medication including the anticonvulsant pregabaline. There are no high-quality data on the interaction between oxycodone and (neuropathic pain) medication on the ventilatory control system. Case reports and randomized studies show that pregabalin induces respiratory depression when combined with opioids. Some alternatives to pregabalin may have a better safety profile. One such alternative is lacosamide, an antiepileptic with a different mode of action than pregabalin, and effective in the treatment of neuropathic pain. The hypothesis is that in contrast to lacosamide, pregabalin will increase the respiratory depressant effect of low-dose oxycodone.\n\nThe objective of the study is to quantify the effect of pregabalin and lacosamide on oxycodone-induced respiratory depression.\n\n24 participants will be screened beforehand if subjects meet the inclusion and exclusion criteria. If so, the subjects will visit the hospital twice. On both occasions, participants will take a 10 mg oxycodone tablet and 90 minutes after a capsule of pregabalin or lacosamide. The order of visits will be randomized. During the visits, at set time points the hypercapnic ventilatory response will be measured, relief of nociception, pupil diameter and several side effects other than respiratory depression. There will be a washout period of 7 days between study visits with the study ending after 2 visits.\n\nAmendment:\n\nIn order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone was added as a visit 3. Since the procedures in this third arm will be identical to the two blinded arms, no changes will be made to any of the procedures apart from not administering any lacosamide or pregabalin.', 'detailedDescription': 'Opioids are commonly prescribed for moderate to severe pain. While initially intended for moderate to severe acute and cancer pain, opioids are currently frequently considered and prescribed in chronic noncancer pain. Due to the large increase in opioid prescription rate, the number of unintentional drug overdoses is rapidly increasing, not only in the Unites States but also in the Netherlands. A potential lethal consequence of an opioid overdose is opioid-induced respiratory depression. Additionally, it is well known that opioids are often used (and abused) in combination with other legal or illicit substances, for example alcohol, benzodiazepines, cannabis, neuropathic pain medication including the anticonvulsant pregabalin. There are no high-quality data on the interaction between oxycodone and (neuropathic pain) medication on the ventilatory control system. Case reports and randomized studies show that pregabalin induces respiratory depression when combined with opioids. Some alternatives to pregabalin may have a better safety profile. One such alternative is lacosamide, an antiepileptic with a different mode of action than pregabalin, and effective in the treatment of neuropathic pain. The hypothesis is that in contrast to lacosamide, pregabalin will increase the respiratory depressant effect of low-dose oxycodone.\n\nThe objective of the study is to quantify the effect of pregabalin and lacosamide on oxycodone-induced respiratory depression.\n\n24 participants will be screened beforehand if the subject meets the inclusion and exclusion criteria. If so, the subjects will visit the hospital twice. On both occasions, participants will be sober and take a 10 mg oxycodone tablet and 90 minutes after a capsule of pregabalin or lacosamide. The order of visits will be randomized using a randomisation list made in R by an independent investigator not involved in data acquisition. Upon arrival in the laboratory, a urinary drug test and breath alcohol test will be performed. When these tests are positive, the subject is excluded from further participation. An intravenous access line will be placed in the left or right arm/hand for fluid administration (NaCl/Glucose 50-100 ml/h). Next, the first hypercapnic ventilatory responses (HCVR) will be obtained (t = -30 min). This is the pre-dug baseline measurement. At t = 0, the subjects will next receive a 10 mg oxycodone immediate release tablet that the subjects will swallow with 100 mL water. Next, the HCVRs at 1-hour intervals will be obtained until 8 hours after oxycodone intake. At t = 90 min the subject will ingest a pregabalin or lacosamide tablet (150 mg). At set time points the hypercapnic ventilatory response will be measured, relief of nociception, pupil diameter and several side effects other than respiratory depression such as sedation, nausea and vomiting. There will be a washout period of 7 days between study visits with the study ending after 2 visits.\n\nBreathing tests: Breathing tests are so-called rebreathing tests in which subjects inhale 7% CO2 in oxygen from a 4-6 L rebreathing bag. By rebreathing carbon dioxide for 3-5 minutes the hypercapnic ventilatory response will be obtained. Ventilation will be measured via the pneumotachograph system.\n\nElectrical pain test: A locally designed and manufactured transcutaneous electrical stimulation device is used to create a constant current electrical stimulus train (stimulation at 20 Hz, pulse duration 0.2 ms). The device is attached to two surface electrodes that are applied on the skin over the tibial bone of the non-dominant side. The current over the electrodes is increased from 0 mA at a rate of 0.5 mA/s, to a maximum of 128 mA. The subjects are instructed to indicate when the stimulation becomes painful (electrical pain threshold, EPTh) by pressing a button on a control box. By pressing a second button, the subjects will end the stimulus train when the pain is perceived as intolerable (electrical pain tolerance, EPTol).\n\nPressure pain test: a pressure pain stimulus will be applied on the skin area (1 cm2) between thumb and index finger, by using the Wagner Instruments FDN 200 Algometer. Subjects will indicate when the pressure stimulus becomes painful (pain threshold) after which the stimulus is stopped. The pressure necessary to induce pain will be recorded. The pressure pain test will follow the electrical pain test by 5-10 min.\n\nQuestionnaires: the subjects will be queried using Visual Analogue Scales from 0-10 cm (range from no effect to most severe effect), for sedation, nausea and vomiting. Additionally, the occurrences of vomiting will be counted.\n\nPupil diameter: At 30-min intervals, the pupil diameter will be measured using a handheld pupillometer (Neuroptics PLR-3000 pupillometer).\n\nAmendment:\n\nIn the study, the effect of two drugs are compared, lacosamide and pregabalin, on top of 10 mg oxycodone, on the ventilatory control system. In order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone was added. The reason for this is many-fold:\n\n1. It will give an indication of the effect of 10 mg oxycodone on the hypercapnic ventilatory response;\n2. It will allow an indication of any difference in effect relative to oxycodone + lacosamide and oxycodone + pregabalin. Note that a formal statistical analysis between just oxycodone and oxycodone + lacosamide or oxycodone + pregabalin will not be performed. The just oxycodone data will be presented as mean ± 95% confidence interval and there will be visually determined whether the mean data from oxycodone + lacosamide and oxycodone + pregabalin fall out of the confidence interval of just oxycodone;\n\nSince the procedures in this third arm will be identical to the two blinded arms, there will be no change to any of the procedures apart from not administering any lacosamide or pregabalin. Hence, there are no other changes to the protocol than the addition of one additional open label arm.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* aged 18-45 years,\n* body mass index \\< 30 kg.m-2,\n* able to understand the written informed consent form,\n* able to communicate with the staff,\n* able and willing to complete the study procedures,\n* signed the informed consent form.\n\nExclusion Criteria:\n\n* Presence or history of any medical or psychiatric disease (incl. a history of substance abuse, anxiety, or the presence of a painful syndrome such as fibromyalgia);\n* Use of any medication in the three months prior to the study which may influence the outcome of the study as judged by the investigator;\n* Use of more than 21 alcohol units per week;\n* A positive urinary drug test or a breath alcohol test at screening or on the morning of the experiment;\n* Pregnancy, lactating or a positive pregnancy test on the morning of the experiment;\n* Participation in another drug trial in the 60 days prior to dosing.'}, 'identificationModule': {'nctId': 'NCT05598905', 'acronym': 'POLO', 'briefTitle': 'Combined Effect of Pregabalin and Oxycodone, and Lacosamide and Oxycodone, on Breathing', 'organization': {'class': 'OTHER', 'fullName': 'Leiden University Medical Center'}, 'officialTitle': 'Combined Effect of Pregabalin and Oxycodone, and Lacosamide and Oxycodone, on Breathing: an Exploratory Study in Healthy Volunteers (The Polo Study)', 'orgStudyIdInfo': {'id': 'P22.044'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Oxycodone + Pregabalin', 'description': 'Participants will visit twice. On one visit they will take a 10mg oxycodone tablet and 90 minutes later a 150mg pregabaline capsule.', 'interventionNames': ['Drug: Pregabalin 150mg', 'Drug: Oxycodone 10mg']}, {'type': 'EXPERIMENTAL', 'label': 'Oxycodone + Lacosamide', 'description': 'Participants will visit twice. On one visit they will take a 10mg oxycodone tablet and 90 minutes later a 150mg Lacosamide capsule.', 'interventionNames': ['Drug: Oxycodone 10mg', 'Drug: Lacosamide 150 mg']}, {'type': 'OTHER', 'label': 'Oxycodone', 'description': 'Amendment:\n\none open label arm.\n\nIn order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone as a visit 3 was added.', 'interventionNames': ['Drug: Oxycodone 10mg']}], 'interventions': [{'name': 'Pregabalin 150mg', 'type': 'DRUG', 'otherNames': ['Lyrica capsule 150 mg'], 'description': 'one capsule of 150mg 90 minutes after 10mg of oxycodone', 'armGroupLabels': ['Oxycodone + Pregabalin']}, {'name': 'Oxycodone 10mg', 'type': 'DRUG', 'otherNames': ['Oxycodone tablet 10 mg'], 'description': 'one 10mg tablet', 'armGroupLabels': ['Oxycodone', 'Oxycodone + Lacosamide', 'Oxycodone + Pregabalin']}, {'name': 'Lacosamide 150 mg', 'type': 'DRUG', 'otherNames': ['Vimpat 150 mg capsule'], 'description': 'one capsule of 150mg 90 minutes after 10mg of oxycodone', 'armGroupLabels': ['Oxycodone + Lacosamide']}]}, 'contactsLocationsModule': {'locations': [{'zip': '2333 ZA', 'city': 'Leiden', 'state': 'South Holland', 'country': 'Netherlands', 'facility': 'Leiden University Medical Center', 'geoPoint': {'lat': 52.15833, 'lon': 4.49306}}], 'overallOfficials': [{'name': 'Marieke Niesters, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Leiden University Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Leiden University Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Albert Dahan', 'investigatorAffiliation': 'Leiden University Medical Center'}}}}