Diet and Exercise Plus Metformin to Treat Frailty in Obese Seniors

NCT04221750 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: ENDA-007-19FH-46970
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Frailty; Sarcopenic Obesity; Aging

Outcome Measures

Primary Outcomes (1)

• Change in the modified Physical Performance Test (PPT)

  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.

  6 months

Secondary Outcomes (28)

• Change in muscle strength

  6 months

• Change in gait speed

  6 months

• Change in peak aerobic power

  6 months

• Change in lean body mass

  6 months

• Chang in body fat

  6 months

Study Arms (3)

Lifestyle Therapy plus Metformin

EXPERIMENTAL

Diet-induced weight loss and Exercise Training plus Metformin 1500 mg daily

Behavioral: Lifestyle therapy; Drug: Metformin Hydrochloride

Lifestyle Therapy plus Placebo

PLACEBO COMPARATOR

Diet-induced weight loss and Exercise Training plus Placebo

Behavioral: Lifestyle therapy; Drug: Placebo

Healthy lifestyle plus Metformin

ACTIVE COMPARATOR

Healthy lifestyle and Metformin 1500 mg daily

Drug: Metformin Hydrochloride; Behavioral: Healthy Lifestyle

Interventions

Placebo DRUG

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.

Lifestyle Therapy plus Placebo

Healthy Lifestyle BEHAVIORAL

Group educational sessions that focus on healthy diet, exercise, and social support once a month

Healthy lifestyle plus Metformin

Lifestyle therapy BEHAVIORAL

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

Also known as: Diet-induced weight loss and exercise training

Lifestyle Therapy plus Metformin; Lifestyle Therapy plus Placebo

Metformin Hydrochloride DRUG

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.

Healthy lifestyle plus Metformin; Lifestyle Therapy plus Metformin

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65 - 85 years
• BMI = or \> 30 kg/m2
• Mild to moderate frailty (score of 18 to 31 in the modified Physical Performance Test)
• Stable body weight (plus/minus 2 kg) during the past 6 months
• Sedentary (regular exercise \<1 h/wk or \<2 x/wk for the last 6 months)
• Willing to provide informed consent

You may not qualify if:

• 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
• 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
• 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
• 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
• 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 \[\>14 drinks per week\])
• Severe visual or hearing impairments that would interfere with following directions
• 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
• Uncontrolled hypertension (BP\>160/90 mm Hg)
• History of malignancy during the past 5 years (except non-melanoma skin cancers)
• 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)
• Osteoporosis (T-score -2.5 and below on hip or spine scan) or history of fragility fractures
• Known history of diabetes mellitus or any of the following:
• Fasting blood glucose of 126 mg/dl, or HbA1c of 6.5% or \>
• Terminal illness with life expectancy less than 12 months, as determined by a physician
• Use of any drugs or natural products designed to induce weight loss within past three months

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Michael E. DeBakey VA Medical Center: collaborator
• Baylor College of Medicine: collaborator

Study Sites (1)

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

Location

MeSH Terms

Conditions

Frailty

Interventions

Exercise; Metformin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Dennis T Villareal, MD

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 9, 2020
• Study Start: May 14, 2021
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)