Effect of Metformin on Frailty in 12 Subjects

NCT03451006 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-003088
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether chronic metformin administration will improve longevity of the cell, improves its machinery by reducing aging-related biochemical parameters and thereby improving physical performance, as measured by short physical performance battery test.

Conditions

Aging; Inflammation; Frailty

Outcome Measures

Primary Outcomes (6)

• Change in Frailty

  Frailty will be measured by the Short Physical Performance Battery (SPPB). The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance). Frailty is defined as a score of \<9.

  Baseline, 12 months

• Change in Balance Score Standing With Feet Close Together

  This measure is part of the SPPB. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.

  Baseline, 12 months

• Change in Balance Score Standing in Semi Tandem Position

  This measure is part of the SPPB. The semi tandem position is the heel of one foot place by the big toe of the other foot. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.

  Baseline, 12 months

• Change in Balance Score Standing in Full Tandem Position

  This measure is part of the SPPB. The full tandem position is with the feet directly in front of each other. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.

  Baseline, 12 months

• Change in Gait Speed

  This measure is part of the SPPB. Subjects will be asked to walk 8 feet or 2.44 meters at their usual pace. They will be allowed to use a cane or other walking aid if it is their custom. Scores range from 0 = could not do to 4 =\<3.1 seconds.

  Baseline, 12 months

• Change in Score, Standing Test From Chair

  This measure is part of the SPPB. Subjects will be asked to try to stand up from a chair 5 times with arms folded across their chest, and will be timed. Scores range from 0 to 4, with 0 = unable to stand without using arms, and 4 = completing 5 stands in \<11.1 seconds.

  Baseline,12 months

Secondary Outcomes (5)

• Change in Interleukin 6 (pg/ml)

  Baseline, 12 months

• Change in Matrix Metalloproteinase (ng/ml)

  Baseline, 12 months

• Change in Plasminogen Activator Inhibitor

  Baseline, 12 months

• Change in Monocyte Chemotactic Protein-1

  Baseline, 12 months

• Change in Activin

  Baseline, 12 months

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin 500mg tablet by mouth, every 6 to 8 hours for one year

Drug: Metformin

Placebo

ACTIVE COMPARATOR

Placebo by mouth every 6 to 8 hours for one year

Drug: Placebo

Interventions

Metformin DRUG

Oral metformin (up to 2gm) will be given in divided doses

Metformin

Placebo DRUG

Oral Placebo will be given in divided doses

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 60 years
• Stable CAD
• Prediabetes (one of the following criteria should be met)
• Fasting plasma glucose: 100-126 mg/dL
• HbA1C: 5.7-6.4
• Frailty (Short Physical Performance Battery: Score \<9)
• Able to return for follow-up
• Written informed consent

You may not qualify if:

• Pre-existing or new-onset diabetes
• Any active malignancy, hematological disorder, post organ transplant, immunocompromised
• Cancer requiring treatment in the past 3 years (other than non-melanoma skin cancer)
• Dementia \[mini mental state examination (MMSE \<20)\]
• Disability (need for assistance in \>2 of any six activities on Katz activities of daily living (ADL)46
• Prior stroke with disability
• Acute coronary syndrome \<3months or participating in cardiac rehabilitation
• Severe Parkinson's
• Hepatic insufficiency and/or chronic liver disease (cirrhosis)
• Chronic kidney disease (GFR \< 45 mL/min)
• Taking metformin for any indication
• Acute alcohol intoxication
• Known hypersensitivity to metformin hydrochloride
• Acute/chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Inflammation; Frailty

Interventions

Metformin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Study was terminated due to recruitment being difficult and not achieved.

Results Point of Contact

• Title: Mandeep Singh, M.D.
• Organization: Mayo Clinic

Singh.Mandeep@mayo.edu

507-255-2398

Study Officials

• Mandeep Singh

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Arms Assigned interventions Placebo Comparator: Metformin Chronic metformin administration through augmentation of cellular regeneration and reduction of senescence will improve frailty and physical functioning as studied by the short physical performance battery (SPPB) test. Drug: Metformin versus placebo This will be a pilot, feasibility study. Twelve subjects ≥60 years with stable CAD and prediabetes, who score \<9 on SPPB test will be randomized to receive up to 2gm of oral metformin or placebo for 12 months. Placebo comparator: Placebo Placebo will be compared to chronic metformin administration Drug: Metformin versus placebo This will be a pilot, feasibility study. Twelve subjects ≥60 years with stable CAD and prediabetes, who score \<9 on SPPB test will be randomized to receive up to 2gm of oral metformin or placebo for 12 months.

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: March 1, 2018
• Study Start: May 24, 2018
• Primary Completion: December 16, 2021
• Study Completion: December 16, 2021
• Last Updated: November 17, 2022
• Results First Posted: November 17, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)