Genomic Outcomes of Metformin

NCT02986659 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB00034977
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Medical scientists have found that people with diabetes who take the drug Metformin have less age-related disease than those taking other treatments and researchers believe it may prevent numerous diseases and conditions that effect older people. In addition, metformin extends lifespan in some animal models of human disease. The purpose of this study is to see if taking Metformin causes changes in blood cells consistent with improved health and longevity in people who do not have diabetes. In this study Metformin will be compared to placebo. A placebo is a substance, like a sugar pill, that is not thought to have any effect on a participants disease or condition. In this study participants will either receive the active study medication, Metformin or placebo which is not active. Placebos are used in research studies to see if the drug being studied really does have an effect.

Conditions

Coronary Artery Disease; Mild Cognitive Impairment; Obesity, Abdominal; Hypertension

Outcome Measures

Primary Outcomes (2)

• Change in Eigengene Scores

  Part of blood sample analysis will give results for Individual methylation sites and transcripts, especially the eigengenes of autophage, oxidative phosphorylation and protein synthesis networks Methylomic and transcriptomic profiles in monocytes. All of the results for these measures will be aggregated into an eigengene score. The eigengene score is a summary measure of a group of correlated genes. This score may indicate status of a biological function. In this analysis, the observed range of values were from -0.48 to 0.66. A lower score means downregulation of the gene group, while a higher score upregulation. No theoretical minimum or maximum value exist for this assay.

  baseline through 12 weeks

• Change in Eigengene Scores

  Part of blood sample analysis will give results for Individual methylation sites and transcripts, especially the eigengenes of autophage, oxidative phosphorylation and protein synthesis networks Methylomic and transcriptomic profiles in monocytes. All of the results for these measures will be aggregated into an eigengene score. The eigengene score is a summary measure of a group of correlated genes. This score may indicate status of a biological function. In this analysis, the observed range of values were from -0.48 to 0.66. A lower score means downregulation of the gene group, while a higher score upregulation. No theoretical minimum or maximum value exist for this assay.

  baseline through 24 weeks

Secondary Outcomes (6)

• Functional Measures--macroautophagy

  baseline through 12 weeks, 12 weeks through 24 weeks

• Functional Measures--microautophagy

  Baseline through 12 weeks, 12 weeks through 24 weeks

• Functional Measures--chaperone-mediated Autophagy

  Baseline through 12 weeks, 12 weeks through 24 weeks

• Mitochondria Function: Respiratory Control Ratio (RCR)

  Baseline through 12 weeks, 12 weeks through 24 weeks

• Mitochondria Function: State 3 (Maximal Oxygen Consumption Rate)

  Baseline through 12 weeks, 12 weeks through 24 weeks

Other Outcomes (14)

• Vital Signs

  Baseline through 12 weeks, 12 weeks through 24 weeks

• Change in Expanded Short Physical Performance Battery (eSPPB)

  From baseline through 12 weeks

• Change in Expanded Short Physical Performance Battery (eSPPB)

  From 12 weeks through 24 weeks

Study Arms (2)

Metformin then Placebo

ACTIVE COMPARATOR

Metformin dosing at 425, 850 and 1700 mg with GLUCOPHAGE® (metformin hydrochloride) Tablets. Treatment with metformin will be initiated at a dose of 425 mg (half pill) taken orally once a day at night for 7 days. After the week, the participant will be called to assess tolerance and will be asked to increase dose to one pill at night at a dose of 850 mg for one week. At the end of the second week, participants will be called again and if they tolerated the second dose, they will be asked to take two 850 mg pills, one in the morning and one at night, for a total dose of 1700 mg which is within the range of the usual effective dose of 1500 to 2000 mg/day for the remainder of the 3 months. Will then cross over to 3 months on placebo.

Drug: Metformin; Drug: Placebo

Placebo then Metormin

PLACEBO COMPARATOR

Dietary Supplement: Placebo with Methylcellulose capsules. Treatment with placebo will be initiated at a dose of a half pill taken orally once a day at night for 7 days. After the week, the participant will be called to assess tolerance and will be asked to increase dose to one pill at night for one week. At the end of the second week, participants will be called again and if they tolerated the second dose, they will be asked to take two pills, one in the morning and one at night for the remainder of the 3 months. After 3 months on placebo, participants will then cross over to 3 months of metformin as described in the other arm.

Drug: Metformin; Drug: Placebo

Interventions

Metformin DRUG

Metformin then Placebo; Placebo then Metormin

Placebo DRUG

Metformin then Placebo; Placebo then Metormin

Eligibility Criteria

• Age: 65 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65 - 79
• Must meet criteria from one or more of the following groups:
• Group 1 (Can have 1 or 2 of these, but not all 3)
• History of coronary artery disease (MI/heart attack, stroke, heart failure, or peripheral artery disease)
• Cancer, with no active treatment in the last year
• MCI (MoCA \>18\<26 -inclusive of 1 point if \<12 years of education Group 2
• Decline physical function (walking speed \< 1 m/s) Group 3 (Either or both)
• Abdominal obesity (\>88cm women, \>102cm men) AND hypertension (treated or resting blood pressure \>140/90
• Abdominal obesity (\>88cm women, \>102cm men) AND hyperlipidemia (treated or fasting total cholesterol \>240 English literacy Willing to provide informed consent

You may not qualify if:

• eGFR \<45
• Type 2 diabetes (HbA1c\>6.5) or type 1 diabetes
• Any tobacco or nicotine product use in the past year
• Low vitamin B12 Levels (\< 300 pg/mL)
• Self-reported severe difficulty or inability to walk 400m or climb 10 steps (from Q 2 and 19 on PAT-D)
• Self-reported difficulty or inability to perform basic ADL functions (from Q 10, 13, 14, 16 on PAT-D)
• Excessive alcohol use (\>14 drinks/week)
• Cancer requiring treatment in past year (except skin)
• Dementia - diagnosed and/or MoCA score \<18
• Parkinson's or other neurological disease
• Chronic liver disease or cirrhosis
• End stage renal disease or on dialysis
• Rheumatic conditions (Rheumatoid arthritis, lupus, and any other autoimmune disease the -PI deems them to be ineligible for)
• Thyroid problems the PI deems them to be ineligible for
• Gout

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Wake Forest Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease; Cognitive Dysfunction; Obesity, Abdominal; Hypertension

Interventions

Metformin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Jingzhong Ding, PhD
• Organization: Atrium Health Wake Forest Baptist

jding@wakehealth.edu

336-713-8601

Study Officials

• Jingzhong Ding, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: December 8, 2016
• Study Start: August 3, 2016
• Primary Completion: November 15, 2018
• Study Completion: November 15, 2018
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)