Ignite Creation Date:
2025-12-24 @ 4:54 PM
Ignite Modification Date:
2025-12-27 @ 4:56 AM
Study NCT ID:
NCT07294950
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-19
First Post:
2025-11-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: Recovery Effects After Semaglutide Termination
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009765', 'term': 'Obesity'}, {'id': 'D001836', 'term': 'Body Weight Changes'}], 'ancestors': [{'id': 'D050177', 'term': 'Overweight'}, {'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 98}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-01-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'completionDateStruct': {'date': '2029-05', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-15', 'studyFirstSubmitDate': '2025-11-17', 'studyFirstSubmitQcDate': '2025-12-15', 'lastUpdatePostDateStruct': {'date': '2025-12-19', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-12-19', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2028-09', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Changes in body mass index (BMI)', 'timeFrame': '32 weeks', 'description': 'Changes in BMI \\[calculated as weight / height2 (in kg/m2)\\] between baseline visit 1 (semaglutide discontinuation) and 5 (16-weeks after complete semaglutide withdrawal) will be compared between the study groups'}, {'measure': 'Changes in waist circumference', 'timeFrame': '32 weeks', 'description': 'Changes in waist circumference between baseline visit 1 (semaglutide discontinuation) and 5 (16-weeks after complete semaglutide withdrawal) will be compared between the study groups'}], 'primaryOutcomes': [{'measure': 'Differences in changes in body weight between each study group', 'timeFrame': '32 weeks', 'description': 'Differences in body weight change (%) between baseline visit 1 (semaglutide discontinuation) and 5 (16-weeks after complete semaglutide withdrawal) will be compared between the study groups'}], 'secondaryOutcomes': [{'measure': 'Differences in 24-h systolic BP levels between each study group', 'timeFrame': '32 weeks', 'description': 'Systolic BP will be assessed as the difference in 24-h ambulatory systolic BP between the study groups at visit 5 (16-weeks after complete semaglutide withdrawal)'}, {'measure': 'Differences in fasting ghrelin between each study group', 'timeFrame': '32 weeks', 'description': 'Differences in fasting ghrelin between the study groups will be assessed at week 5 (16-weeks after complete semaglutide withdrawal)'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Randomized controlled trial', 'Interventional'], 'conditions': ['Obesity (Disorder)', 'Weight Change', 'Blood Pressure Monitoring', 'Appetite Regulation']}, 'descriptionModule': {'briefSummary': 'Semaglutide is a medication from the class of drugs called glucagon-like peptide-1 agonists that promote weight loss. There is little clinical data on the best strategy to achieve weight maintenance following weight reduction induced by semaglutide. For people who need to discontinue treatment, it is unknown whether the weight regain, its accompanied health benefits could be ameliorated with a gradual reduction in semaglutide. The investigators will study if a gradual reduction of semaglutide is associated with different heart risk profile and hormones involved in energy regulation as compared to immediate treatment cessation.', 'detailedDescription': 'It is known that semaglutide induces a supra-physiologic agonism of GLP-1 receptors on central nervous system receptors associated with hedonic eating which likely promotes a homeostatic response (i.e. adaptation) related to appetite control. This concept raises the question of whether a gradual de-escalation of GLP-1RA could ameliorate the tendency for weight regain/cardiometabolic deterioration and compensatory changes in energy balance regulation following cessation of treatment.Thus, the investigators propose an open-label, parallel-arm, randomized controlled trial to determine whether a gradual dose reduction in semaglutide prior to complete discontinuation is associated with differential changes in weight and cardiometabolic profile (blood pressure homeostasis and energy balance regulatory hormones) as compared to immediate treatment cessation in individuals living with obesity without pre-existing cardiovascular disease who are receiving semaglutide for weight management.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Men and women with previously diagnosed BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and adiposity-related complications (such as osteoarthritis, nonalcoholic liver disease, sleep apnea, and hypertension) without preexisting cardiovascular disease or type 2 diabetes.\n* Age 18 - 75 years inclusive\n* Ongoing weight-loss treatment consisting of weekly subcutaneous semaglutide at minimum dose of 1 mg/weekly with documented weight reduction of at least 10% of pre-treatment body weight\n* Stable weight over past 12 weeks (less than 5% change in body weight) (self-reported)\n* Ability to read and understand English\n\nExclusion Criteria:\n\n* Previously diagnosed cardiovascular disease defined as previous myocardial infarction, previous stroke, or symptomatic peripheral arterial disease.\n* Currently pregnant or lactating\n* Previously diagnosed type 2 diabetes\n* Use of any other pharmacological treatment for weight-loss\n* Previous surgical treatment for weight loss such as gastric bypass or gastric band\n* Any history of eating disorder\n* Renal dysfunction as evidenced by estimated glomerular filtration rate \\< 25 ml/min by CKD-EPI Creatinine Equation\n* New York Heart Association class II-IV heart failure\n* Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, or previous liver transplant) or transaminases \\>2.5X the upper limit of normal\n* Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)\n* Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2\n* Any other factor likely to limit adherence to the study, in the opinion of the investigators'}, 'identificationModule': {'nctId': 'NCT07294950', 'acronym': 'REST', 'briefTitle': 'Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: Recovery Effects After Semaglutide Termination', 'organization': {'class': 'OTHER', 'fullName': 'Mount Sinai Hospital, Canada'}, 'officialTitle': 'Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: a Randomized Controlled Trial Comparing Gradual Dose Reduction With Immediate Treatment Cessation.', 'orgStudyIdInfo': {'id': 'REB#1360'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Gradual dose reduction of semaglutide', 'description': 'Participants will reduce semaglutide dosage by 25% every 4-weeks until complete treatment cessation at week 16', 'interventionNames': ['Drug: Gradual dose reduction of semaglutide']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Cessation of semaglutide', 'description': 'Participants will discontinue treatment at once at week 16', 'interventionNames': ['Drug: Abrupt cessation of semaglutide']}], 'interventions': [{'name': 'Gradual dose reduction of semaglutide', 'type': 'DRUG', 'description': 'Pparticipants will reduce semaglutide dosage by 25% every 4-weeks until complete treatment cessation at week 16', 'armGroupLabels': ['Gradual dose reduction of semaglutide']}, {'name': 'Abrupt cessation of semaglutide', 'type': 'DRUG', 'description': 'Cessation of semaglutide at 16-weeks', 'armGroupLabels': ['Cessation of semaglutide']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M5T 3L9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'contacts': [{'name': 'Caroline K Kramer, MD PhD', 'role': 'CONTACT', 'email': 'caroline.kramer@sinaihealth.ca', 'phone': '+14165864800 ext 7628'}], 'facility': 'Leadership Sinai Centre for Diabetes', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'centralContacts': [{'name': 'Caroline K Kramer, MD PhD', 'role': 'CONTACT', 'email': 'caroline.kramer@sinaihealth.ca', 'phone': '+1 4165864800 ext 7628'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mount Sinai Hospital, Canada', 'class': 'OTHER'}, 'collaborators': [{'name': 'Heart and Stroke Foundation of Canada', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}