- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02570672
Metformin for Preventing Frailty in High-risk Older Adults
Study Overview
Detailed Description
Physical frailty is a geriatric syndrome that leads to poor health outcomes such as falls, disability, institutionalization, and death. The prevalence of frailty is estimated to be 7-15% among community-dwelling older U.S. adults. The associated costs of frailty were estimated to be more than $18 billion in 2000 and these will continue to increase over the next two decades. Thus, an increasingly frail older population will have major implications for the demand for health care services, including hospital usage, home care, and long-term care.
Data from several studies have suggested strong roles for diabetes and insulin resistance, which are associated with increased inflammation, in the physiological basis of frailty. The investigators' recent epidemiological research with a community-based population of older adults showed that diabetes was the most significant predictor of frailty onset and worsening over time. While the importance of frailty and its impact on an aging U.S. society have been widely recognized, to date there are no effective interventions to prevent or treat frailty. Therefore, the major goal of this study is to test a drug with insulin-sensitizing and anti-inflammatory properties, such as metformin, as a novel intervention for frailty prevention.
The investigators hypothesize that metformin will lead to reduced inflammation and insulin resistance present in older glucose-intolerant subjects and that these changes will consequently prevent the onset and/or progression of frailty in this sub-population of older adults. Subjects with impaired glucose intolerance will be enrolled in this study because this group encompasses approximately 1/3rd of the older population, this group is at increased risk for developing diabetes and frailty, and is the most likely to benefit from a potential anti-inflammatory and insulin-sensitizing intervention.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Texas
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San Antonio, Texas, United States, 78229
- University of Texas Health Science Center at San Antonio
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women
- All ethnic groups
- Age 65 and older
- Community-dwelling
- Pre-diabetic based on oral glucose tolerance test with 2 hour values of 140 - 199 mg/dL after an oral glucose load, and no diagnosis of diabetes in the past 12 months
- Subjects must have the following laboratory values: Hematocrit ≥ 33%, aspartate aminotransferase < 2 X upper limit of normal, alanine aminotransferase < 2 X upper limit of normal, alkaline phosphatase < 2 X upper limit of normal, normal urinalysis (no clinically significant white blood cells, red blood cells or bacteria), platelets ≥ 100,000, prothrombin time < 15 seconds and partial thromboplastin time < 40 seconds, glomerular filtration rate (GFR) ≥ 45ml/min and urine protein ≤ 100 mg/dL by lab urinalysis.
Exclusion Criteria:
- Characterized as frail, defined as the presence of 3 or more of: 1) weak hand grip strength, 2) slow walking speed, 3) low physical activity, 4) unintentional weight loss of ≥ 10 pounds over the past year, 5) self-reported exhaustion
- Resident of nursing home or long-term care facility
- Subjects with diabetes with range fasting glucose in diabetes range (≥ 126 mg/dL), or 2-hour glucose within diabetes range on OGTT (≥ 200 mg/dL).
- Subjects taking drugs known to affect glucose homeostasis
- Untreated depression or Geriatric Depression Scale (GDS) score on 15-item scale >7
- Diagnosis of any disabling neurologic disease Parkinson's Disease, Amyotrophic Lateral Sclerosis, multiple sclerosis, cerebrovascular accident with residual deficits (muscle weakness or gait disorder), severe neuropathy, diagnosis of dementia or Mini-mental State Exam (MMSE) score <24, cognitive impairment due to any reason such that the patient is unable to provide informed consent.
- History of moderate-severe heart disease (New York Heart Classification greater than grade II) or pulmonary disease (dyspnea on exertion upon climbing one flight of stairs or less; abnormal breath sounds on auscultation)
- Poorly controlled hypertension (systolic >160 mmHg, diastolic >100 mmHg)
- Peripheral arterial disease (history of claudication)
- Moderate to severe valvular heart disease
- Subjects who have been treated with long term (>30 days) systemic steroids, anabolic steroids, growth hormone or immunosuppresants within the last 6 months. Males with a medical history of testosterone deficiency who are on a stable dose of testosterone replacement (for ≥ 3 months) are allowed.
- Subjects who have been treated with short term (<30 days) systemic steroids, anabolic steroids, growth hormone or immunosuppressants within the last 1 month.
- Chronic inflammatory condition, autoimmune disease, or infectious processes (e.g., active tuberculosis, Human Immunodeficiency Virus, rheumatoid arthritis, systemic lupus erythematosus, acute or chronic hepatitis B or C)
- Active tobacco use (within 6 months)
- Illicit drug use
- Active malignancy, non-skin
- Disease or condition likely to cause death within 5 years
- Hypersensitivity to metformin or pioglitazone
- Any disease or condition considered to be exclusionary based on the clinical opinion and discretion of the PI
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Metformin
Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated)
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Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.
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Placebo Comparator: Placebo
Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo.
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Subjects will randomized to placebo will receive placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frailty composite measure
Time Frame: 2 years
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Frailty will be defined using validated standardized criteria (Fried et al., J Geron.
2001 Mar;56(3):M146-56).
The frailty score will be measured every 6 months as 0 through 5 of the following 5 frailty characteristics: 1) unintentional weight loss (>= 10 pounds) in last year; 2) self reported exhaustion based on the Geriatric Depression Scale item, "Do you feel full of energy?;" 3) muscle weakness based on hand grip strength measurement (standardized cut points are published); 4) slow gait speed based on 10-foot walk (standardized cut points are published); and 5) low physical activity measured in kilocalories/week based on the Minnesota Leisure Time Questionnaire (standardized cutpoints are published).
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2 years
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Sara E Espinoza, M.D., Associate Professor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HSC20150237H
- 1R01AG052697-01A1 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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