A Double-Blind, Placebo-Controlled Trial of Anti-Aging, Pro-Autophagy Effects of Metformin in Adults With Prediabetes

NCT03309007 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 17-214
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot and feasibility study is to investigate the effects of a short course of metformin therapy on a surrogate marker of cellular senescence and autophagy among adult patients with prediabetes. The overall hypothesis is that metformin will have beneficial effects on longevity and quality of life by inducing autophagy downstream of activating adenosine monophosphate-activated protein kinase (AMPK) and inhibiting mechanistic target of rapamycin (mTOR) through potential effects of reduced inflammation, reduced degeneration of muscle and tendon tissue, antineoplastic effects, reduced obesity and hyperglycemia, preserved cardiovascular functions, and/or the prevention of neurodegeneration (such as age-associated dementia). This pilot study will address the following aim: Demonstrate that metformin therapy will increase cellular autophagy as an inverse correlate of aging as measured by increases in Microtubule-associated protein 1A/1B-light chain 3 (LC3) scores. Hypothesis 1: In addition to beneficial effects on glycemia, body weight, and body composition, metformin therapy exerts beneficial effects on surrogate measures of autophagy and aging. Primary outcome: Increased levels of LC3 in leukocytes.

Conditions

PreDiabetes; Aging

Keywords

Autophagy

Outcome Measures

Primary Outcomes (1)

• Change in Leucocyte LC3 Score

  During the process of autophagy, autophagosomes engulf cytoplasmic components and concomitantly, the cytosolic form of LC3 (LC3-I) is conjugated to phosphatidyl ethanolamine, resulting in the autophagosomal membrane-bound form (LC3-II). LC3-II is a widely used marker to monitor autophagosome formation by quantitation of the number of LC3-labeled puncta (autophagosomes, or "dots") per cell detected by fluorescence microscopy. An increase in LC3 puncta formation denotes an increase in autophagic activity.

  Data will be collected at 0 and 12 weeks and analyzed within 8 weeks of sample collection.

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin started at 500 mg po twice daily (BID), and then titrated up to 1000 mg po q morning (AM) and 500 po q evening (PM) over the course of 1 month, as tolerated.

Drug: Metformin

Placebo Oral Tablet

PLACEBO COMPARATOR

Near-identical CaCO3 as a Placebo Oral Tablet will be started at 648 mg po BID, and then titrated up to 1296 mg po q AM and 648 mg po q PM over the course of 1 month, as tolerated.

Drug: Placebo Oral Tablet

Interventions

Metformin DRUG

Total daily dose titrated up to 1500 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.

Also known as: Glucophage

Metformin

Placebo Oral Tablet DRUG

Total daily dose titrated up to 1944 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.

Also known as: Calcium Carbonate

Placebo Oral Tablet

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with prediabetes (defined as an A1c of 5.7-6.4%)
• BMI between 27 and 40 kg/m2 (inclusive).

You may not qualify if:

• Prior treatment with metformin or other diabetes medications,
• Pregnancy,
• Significant renal dysfunction (Serum Creatinine \> 1.3 mg/dl for women, \> 1.4 mg/dl for men),
• Severe hepatic dysfunction (aspartate amnotransferease \[AST\] or alanine aminotransferase \[ALT\] \> 3 times the upper limit of normal),
• Ongoing alcohol or substance abuse,
• Inflammatory bowel disease,
• Ongoing glucocorticoid therapy,
• Or inability to render informed consent.

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

University of New Mexico Clincal & Translational Science Center

Albuquerque, New Mexico, 87131, United States

Location

MeSH Terms

Conditions

Prediabetic State

Interventions

Metformin; Calcium Carbonate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Results Point of Contact

• Title: MArk Burge
• Organization: UNewMexico

mburge@salud.unm.edu

5052724658

Study Officials

• Mark R Burge, MD

  Professor Medicine, UNM HSC Endocrinology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the study research pharmacy will have access to the randomization list.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a double-blind, approximate placebo-controlled trial of 12 weeks of metformin vs. CaCO3 (Placebo) among adult patients with prediabetes.

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: October 13, 2017
• Study Start: September 1, 2017
• Primary Completion: August 20, 2020
• Study Completion: August 20, 2020
• Last Updated: December 11, 2023
• Results First Posted: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After the study is completed and published. The data should be available in perpetuity in the University of New Mexico (UNM) Digital Repository.
• Access Criteria: No restrictions.

Locations

US (1)