Ignite Creation Date:
2025-12-24 @ 4:46 PM
Ignite Modification Date:
2025-12-24 @ 4:46 PM
Study NCT ID:
NCT04221750
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-01-22
First Post:
2020-01-02
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Diet and Exercise Plus Metformin to Treat Frailty in Obese Seniors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000073496', 'term': 'Frailty'}], 'ancestors': [{'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D015444', 'term': 'Exercise'}, {'id': 'D008687', 'term': 'Metformin'}], 'ancestors': [{'id': 'D009043', 'term': 'Motor Activity'}, {'id': 'D009068', 'term': 'Movement'}, {'id': 'D009142', 'term': 'Musculoskeletal Physiological Phenomena'}, {'id': 'D055687', 'term': 'Musculoskeletal and Neural Physiological Phenomena'}, {'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2024-09-13', 'size': 134774, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_000.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-01-17T17:15', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Placebo controlled'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 114}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2021-05-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2027-09-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-01-17', 'studyFirstSubmitDate': '2020-01-02', 'studyFirstSubmitQcDate': '2020-01-06', 'lastUpdatePostDateStruct': {'date': '2025-01-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-01-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-09-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'change in Senescent Associated Secretory Phenotype (SASP)', 'timeFrame': '6 months', 'description': 'Measured by immunoassay-based platform; results will be expressed as composite factor score'}], 'primaryOutcomes': [{'measure': 'Change in the modified Physical Performance Test (PPT)', 'timeFrame': '6 months', 'description': 'The Physical Performance Test includes seven standardized tasks (walking 15.2 m \\[50 ft\\], putting on and removing a coat, picking up a penny, standing up from a chair, lifting a book, climbing one flight of stairs, and performing a progressive Romberg test) plus two additional tasks (going up and down four flights of stairs and making a 360-degree turn). The score for each task ranges from 0 to 4, with higher scores indicating better physical performance; a perfect score would be 36.'}], 'secondaryOutcomes': [{'measure': 'Change in muscle strength', 'timeFrame': '6 months', 'description': 'Assessed by biodex dynamometer and1-repetition maximum'}, {'measure': 'Change in gait speed', 'timeFrame': '6 months', 'description': 'Assessed by time need to walk a certain distance'}, {'measure': 'Change in peak aerobic power', 'timeFrame': '6 months', 'description': 'Assessed by indirect calorimetry during a graded exercise test'}, {'measure': 'Change in lean body mass', 'timeFrame': '6 months', 'description': 'Assessed by dual-energy x-ray absorptiometry (DXA)'}, {'measure': 'Chang in body fat', 'timeFrame': '6 months', 'description': 'Assessed by DXA'}, {'measure': 'Change in thigh muscle', 'timeFrame': '6 months', 'description': 'Assessed by magnetic resonance imaging (MRI)'}, {'measure': 'Change in bone microarchitecture', 'timeFrame': '6 months', 'description': 'Assessed by high-resolution peripheral quantitative computed tomograph (HR-pQCT)'}, {'measure': 'Change in bone strength', 'timeFrame': '6 months', 'description': 'Assessed by finite-element analyses'}, {'measure': 'Change in hip, lumbar spine, and wrist bone mineral density (BMD)', 'timeFrame': '6 months', 'description': 'Assessed by DXA'}, {'measure': 'Change in serum C-telopeptide', 'timeFrame': '6 months', 'description': 'Assessed by immunoassay'}, {'measure': 'Change in telomere length', 'timeFrame': '6 months', 'description': 'Assessed by Q-PCR'}, {'measure': 'Change in mood', 'timeFrame': '6 months', 'description': 'Assessed by geriatric depression scale (score range: 0 to 30, where lower scores indicating better mood)'}, {'measure': 'Change in serum procollagen type 1 N propeptide', 'timeFrame': '6 months', 'description': 'Assessed by radioimmunoassay'}, {'measure': 'Change in serum 25-OH vitamin D', 'timeFrame': '6 months', 'description': 'Assessed by immunoassay'}, {'measure': 'Change in serum parathyroid hormone', 'timeFrame': '6 months', 'description': 'Assessed by immunoassay'}, {'measure': 'Change in high-sensitivity c-reactive protein', 'timeFrame': '6 months', 'description': 'Assessed by immunoassay'}, {'measure': 'Change in p16 and other markers of cell arrest', 'timeFrame': '6 months', 'description': 'Assessed by immunohistochemistry'}, {'measure': 'Change in satellite cells and fiber typing', 'timeFrame': '6 months', 'description': 'Assessed by by immunofluorescence'}, {'measure': 'Change in protein expression of senescence associated secretory phenotype', 'timeFrame': '6 months', 'description': 'Assessed by elisa or western blotting'}, {'measure': 'Change in Medical Outcomes 36-Item short form Health survey (SF-36)', 'timeFrame': '6 months', 'description': 'Assessed by Physical component summary and mental component summary score (score range 0 to 100, with higher scores indicating better health status)'}, {'measure': 'Change in Impact of Weight on Quality of Life_Lite (IWQOL-lite) score', 'timeFrame': '6 months', 'description': 'Assessed by IWQO-liteL questionnaire'}, {'measure': 'Change in serum adiponectin', 'timeFrame': '6 months', 'description': 'Assessed by ELISA'}, {'measure': 'Change in serum leptin', 'timeFrame': '6 months', 'description': 'Assessed by ELISA'}, {'measure': 'Change in fasting serum insulin', 'timeFrame': '6 months', 'description': 'Assessed by immunoassay'}, {'measure': 'Change in fasting serum glucose', 'timeFrame': '6 months', 'description': 'Assessed by glucose oxidase method'}, {'measure': 'Change in blood pressure', 'timeFrame': '6 months', 'description': 'Assessed by sphygmomanometry'}, {'measure': 'Change in serum lipids', 'timeFrame': '6 months', 'description': 'Assessed by automated enzymatic/colorimetric assays'}, {'measure': 'Change in insulin growth factor 1', 'timeFrame': '6 months', 'description': 'Assessed by immunoassay'}, {'measure': 'Change in Cognitive composite scores', 'timeFrame': '6 months', 'description': 'Using cognitive toolbox which yields the following summary scores: Cognitive Function\n\nComposite Score, Fluid Cognition Composite Score, and Crystallized Cognition Composite Score (score range: -3 to +3 for each with higher scores indicating better cognitive status'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Frailty', 'Sarcopenic Obesity', 'Aging']}, 'descriptionModule': {'briefSummary': 'The continuing increase in prevalence of obesity in older adults including many older Veterans has become a major health concern. The clinical trial will test the central hypothesis that a multicomponent intervention consisting of lifestyle therapy (diet-induced weight loss and exercise training) plus metformin will be the most effective strategy for reversing sarcopenic obesity and frailty in older Veterans with obesity.', 'detailedDescription': "The growing prevalence of obesity in older adults including many older Veterans, has become a major concern in the US already strained health care system in general and in the VA in particular. In older adults, obesity exacerbates the age-related decline in physical function resulting in frailty, decrease in quality of life, loss of independence, and increase in nursing home admissions. The investigators' group demonstrated that weight loss from lifestyle therapy improves physical function and ameliorates frailty but the improvement was modest at best and most obese older adults remained frail. More importantly, there are concerns that the weight-loss induced loss of muscle and bone mass could worsen underlying age-related sarcopenia and osteopenia in the subset of frail obese elderly. Metformin, a biguanide, is a widely available drug used as first line treatment of type 2 diabetes. Animal studies suggest that metformin improves health span and increases lifespan, hence may represent a novel intervention for frailty. Because metformin reduces cellular senescence and senescence-associated phenotype (SASP), it is believed to retard accelerated aging most especially in older adults with obesity. The objective is to conduct a head-head comparative efficacy, placebo controlled, randomized controlled trial to test the hypothesis that lifestyle therapy + metformin for six months will be more effective than lifestyle therapy alone or metformin alone in improving physical function and preventing the weight loss-induced reduction in muscle and bone mass in obese (BMI \\> 30 kg/m2) older (age 65 years) Veterans with physical frailty."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '65 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* BMI = or \\> 30 kg/m2\n* Stable body weight (plus/minus 2 kg) during the past 6 months\n* Sedentary (regular exercise \\<1 h/wk or \\<2 x/wk for the last 6 months)\n* Willing to provide informed consent\n\nExclusion Criteria:\n\n* Any major chronic diseases, or any condition that would interfere with exercise or dietary restriction, or use of metformin, in which exercise, dietary restrictions, or metformin are contraindicated, or that would interfere with interpretation of results\n* Cardiopulmonary disease (e.g. recent MI, unstable angina, stroke) or unstable disease (e.g., NYHA Class III or IV congestive heart failure, severe pulmonary disease requiring steroid pills or the use of supplemental oxygen) that would contraindicate exercise or dietary restriction\n* Severe orthopedic (e.g. awaiting joint replacement) and/or neuromuscular (e.g. multiple sclerosis, active rheumatoid arthritis) disease or impairments that would contraindicate participation in exercise\n* Renal impairment as defined by an estimated glomerular filtration rate (eGFR of less than 30 mL/min/1.73 m2) in which metformin is contraindicated\n* Other significant co-morbid disease that would impair ability to participate in the exercise intervention (e.g. severe psychiatric disorder \\[e.g. bipolar, schizophrenia\\], excess alcohol use \\[\\>14 drinks per week\\])\n* Severe visual or hearing impairments that would interfere with following directions\n* Significant cognitive impairment, defined as a known diagnosis of dementia or positive screening test for dementia using the Mini-Mental State Exam (i.e. MMSE score \\<24)69\n* Uncontrolled hypertension (BP\\>160/90 mm Hg)\n* History of malignancy during the past 5 years (except non-melanoma skin cancers)\n* Current use of bone acting drugs (e.g. use of estrogen, or androgen containing compound,raloxifene, calcitonin, parathyroid hormone during the past year or bisphosphonates during the last two years)\n* Osteoporosis (T-score -2.5 and below on hip or spine scan) or history of fragility fractures\n* Known history of diabetes mellitus or any of the following:\n\n * fasting blood glucose of 126 mg/dl, 2-h blood glucose 200 mg/dl in the OGTT, or HbA1c of 6.5% or \\>\n* Terminal illness with life expectancy less than 12 months, as determined by a physician\n* Use of any drugs or natural products designed to induce weight loss within past three months\n* History of excessive alcohol consumption (e.g. 8 or more drinks a week for women and 15 or more drinks a week for men)\n* Positive exercise stress test for ischemia or any indication for early termination of exercise stress testing\n* Taking metformin or any other glucose lowering drug\n* Lives outside of the study site or is planning to move out of the area in the next 2 years'}, 'identificationModule': {'nctId': 'NCT04221750', 'acronym': 'DEMFOS', 'briefTitle': 'Diet and Exercise Plus Metformin to Treat Frailty in Obese Seniors', 'organization': {'class': 'FED', 'fullName': 'VA Office of Research and Development'}, 'officialTitle': 'Lifestyle Intervention Plus Metformin to Treat Frailty in Older Veterans With Obesity', 'orgStudyIdInfo': {'id': 'ENDA-007-19F'}, 'secondaryIdInfos': [{'id': 'H-46970', 'type': 'OTHER_GRANT', 'domain': 'VA Office of Research and Development'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Lifestyle Therapy plus Metformin', 'description': 'Diet-induced weight loss and Exercise Training plus Metformin 1500 mg daily', 'interventionNames': ['Behavioral: Lifestyle therapy', 'Drug: Metformin Hydrochloride']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Lifestyle Therapy plus Placebo', 'description': 'Diet-induced weight loss and Exercise Training plus Placebo', 'interventionNames': ['Behavioral: Lifestyle therapy', 'Drug: Placebo']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Healthy lifestyle plus Metformin', 'description': 'Healthy lifestyle and Metformin 1500 mg daily', 'interventionNames': ['Drug: Metformin Hydrochloride', 'Behavioral: Healthy Lifestyle']}], 'interventions': [{'name': 'Lifestyle therapy', 'type': 'BEHAVIORAL', 'otherNames': ['Diet-induced weight loss and exercise training'], 'description': 'Weight management program, in which participants are prescribed a balanced diet that provides and energy deficit of 500 to 750 kcal per day to induced \\~10% weight loss plus Supervised combined aerobic and resistance exercise training three times weekly', 'armGroupLabels': ['Lifestyle Therapy plus Metformin', 'Lifestyle Therapy plus Placebo']}, {'name': 'Metformin Hydrochloride', 'type': 'DRUG', 'description': 'Given orally starting at 500 mg (one tablet) taken orally once a day with meals. After a week, the dose of metformin will be increased to 1000 mg (two tablets) daily. After another week, the dose of metformin will be increased to 1500 mg (three tablets) daily.', 'armGroupLabels': ['Healthy lifestyle plus Metformin', 'Lifestyle Therapy plus Metformin']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Given orally starting at 500 mg (one tablet) taken orally once a day with meals. After a week, the dose of placebo will be increased to 1000 mg (two tablets) daily. After another week, the dose of placebo will be increased to 1500 mg (three tablets) daily.', 'armGroupLabels': ['Lifestyle Therapy plus Placebo']}, {'name': 'Healthy Lifestyle', 'type': 'BEHAVIORAL', 'description': 'Group educational sessions that focus on healthy diet, exercise, and social support once a month', 'armGroupLabels': ['Healthy lifestyle plus Metformin']}]}, 'contactsLocationsModule': {'locations': [{'zip': '77030-4211', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Michael E. DeBakey VA Medical Center, Houston, TX', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}], 'overallOfficials': [{'name': 'Dennis T Villareal, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Michael E. DeBakey VA Medical Center, Houston, TX'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': "Publications from this research will be made available to the public through the National Library of Medicine PubMed Central website within one year after the date of publication (guidance is provided on the ORD website).\n\nMEDVAMC will not provide unrestricted, open public access to large scale health related datasets because of re-identification concerns and the obligation to protect Veterans' private information. However, controlled public access will be provided to the greatest extent possible under specific DUAs or other written agreements, and open access will be provided to the final datasets underlying peer-reviewed publications (aggregated data that can be released with privacy and confidentiality risks)."}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'VA Office of Research and Development', 'class': 'FED'}, 'collaborators': [{'name': 'Michael E. DeBakey VA Medical Center', 'class': 'FED'}, {'name': 'Baylor College of Medicine', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}