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Metformin for Preventing Frailty in High-risk Older Adults

Primary Purpose

Frailty

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Metformin

Placebo

About this trial

This is an interventional prevention trial for Frailty

Eligibility Criteria

65 Years - 90 Years (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Texas Health Science Center at San Antonio

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metformin

Placebo

Arm Description

Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated)

Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo.

Outcomes

Primary Outcome Measures

Frailty composite measure

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).

Secondary Outcome Measures

Full Information

NCT ID

NCT02570672

First Posted

September 8, 2015

Last Updated

January 9, 2023

Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

National Institute on Aging (NIA)

1. Study Identification

Unique Protocol Identification Number

NCT02570672

Brief Title

Metformin for Preventing Frailty in High-risk Older Adults

Official Title

Metformin for Preventing Frailty in High-risk Older Adults

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 2016 (Actual)

Primary Completion Date

October 2023 (Anticipated)

Study Completion Date

October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

National Institute on Aging (NIA)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Frailty

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

125 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Experimental

Arm Description

Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo.

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Subjects will randomized to placebo will receive placebo

Primary Outcome Measure Information:

Title

Frailty composite measure

Description

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sara E Espinoza, M.D.

Organizational Affiliation

Associate Professor

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas Health Science Center at San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

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Metformin for Preventing Frailty in High-risk Older Adults

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