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Metformin for Preventing Frailty in High-risk Older Adults

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ClinicalTrials.gov Identifier: NCT02570672
Recruitment Status : Recruiting
First Posted : October 7, 2015
Last Update Posted : November 3, 2020
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Sara Espinoza, The University of Texas Health Science Center at San Antonio

Tracking Information
First Submitted Date  ICMJE September 8, 2015
First Posted Date  ICMJE October 7, 2015
Last Update Posted Date November 3, 2020
Actual Study Start Date  ICMJE April 2016
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2016)
Frailty composite measure [ Time Frame: 2 years ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2015)
Frailty based on Fried criteria [ Time Frame: 2 years ]
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).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Metformin for Preventing Frailty in High-risk Older Adults
Official Title  ICMJE Metformin for Preventing Frailty in High-risk Older Adults
Brief Summary Frailty is a geriatric syndrome which leads to poor health outcomes in older adults, such as falls, disability, hospitalization, institutionalization, and death. Due to the dramatic growth in the U.S. aging population and the health care costs associated with frailty (estimated at more than $18 billion per year), frailty is a major health care problem. There has been little research into potential pharmacologic interventions that would delay or reduce the incidence of frailty. Thus, the major goal of this study is to test metformin as a novel intervention for the prevention of frailty. The investigators propose that diabetes/insulin resistance and inflammation are major contributors to frailty, and that the use of metformin to modulate diabetes/insulin resistance and inflammation will prevent and/or ameliorate the progression of frailty.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Frailty
Intervention  ICMJE
  • Drug: Metformin
    Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.
  • Drug: Placebo
    Subjects will randomized to placebo will receive placebo
Study Arms  ICMJE
  • Experimental: Metformin
    Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated)
    Intervention: Drug: Metformin
  • Placebo Comparator: Placebo
    Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 6, 2015)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, normal electrolytes, normal platelets, prothrombin time and partial thromboplastin time, and normal renal function for the subject's age (defined by a serum creatinine <1.5 mg/dL in males or <1.4 mg/dL in females and creatinine clearance ≥ 60 mL/min).

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 based on American Diabetes Association criteria or currently taking glucose lowering medications
  • Subjects taking drugs known to affect glucose homeostasis
  • Untreated depression or Geriatric Depression Scale 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), diagnosis of dementia or Mini-mental State Exam score <18
  • 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 >170 mmHg, diastolic >105 mmHg)
  • Peripheral arterial disease (history of claudication)
  • Moderate to severe valvular heart disease
  • Subjects who have taken systemic steroids, anabolic steroids, growth hormone or immunosuppressants within 6 months
  • Chronic inflammatory condition, autoimmune disease, or infectious processes (e.g., active tuberculosis, Human Immunodeficiency Virus, rheumatoid arthritis, systemic lupus erythematosus, 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
  • Donated blood within the last 2 months
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years to 90 Years   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alicia Conde, M.A. 210-617-5197
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02570672
Other Study ID Numbers  ICMJE HSC20150237H
1R01AG052697-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sara Espinoza, The University of Texas Health Science Center at San Antonio
Study Sponsor  ICMJE The University of Texas Health Science Center at San Antonio
Collaborators  ICMJE National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Sara E Espinoza, M.D. Associate Professor
PRS Account The University of Texas Health Science Center at San Antonio
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP