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Trial record 3 of 318 for:    PARTNER AND Mayo Clinic

Effect of Metformin on Frailty in 12 Subjects

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ClinicalTrials.gov Identifier: NCT03451006
Recruitment Status : Recruiting
First Posted : March 1, 2018
Last Update Posted : March 21, 2018
Sponsor:
Information provided by (Responsible Party):
Mandeep Singh, Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Aging Inflammation Frailty Drug: Metformin Drug: Placebo Phase 2

Detailed Description:

Heart disease is the number one cause of death in the United States and disproportionately affects older adults, underscoring the need to examine determinants of survivorship. Recognizing this gap, current guidelines lay emphasis to assess frailty, a key construct prevalent in elderly and known to impact their prognosis.Older persons are commonly frail, manifest hyperglycemia and their health span is truncated by illnesses during which physiological declines together with accumulation of additional deficits results in multimorbidity and functional dependence. High incidence of functional decline and stress hyperglycemia in patients with coronary artery disease (CAD) makes pharmacologic manipulation, an attractive strategy to improve frailty and reduce adverse cardiovascular outcomes. Metformin exerts its effect on health span as a calorie restriction-mimetic through inhibition of mitochondrial complex 1 and activation of activated protein kinase (AMP).This drug is safe and has been shown to prolong life in mammals. Metformin by reducing effects of cellular senescence and improving glycemic control may improve the functioning of older adults.

In CAD, cellular senescence and inflammation affect organ dysfunction through interference with tissue homeostasis and regeneration. The deleterious effect of senescence includes pro-inflammatory senescence-associated secretory phenotype (SASP). Normal biological function through alteration in cellular homeostasis and restoration of glycemic control may be achieved by metformin. The phenotypic manifestations of these changes are incompletely characterized as it is yet unknown whether cell-intrinsic regenerative mechanisms can be translated into clinical improvement in physical performance and whether it's chronic administration is safe in older adults. These major gaps in knowledge hinder utilization of metformin as an agent to promote cellular regeneration and to reduce the impact of cellular senescence.

Targeting frail individuals with high levels of inflammation and SASP factors would necessitate identification of predictors of improvement with metformin in tissue inflammation and function. A clinomics approach implementing simultaneous assessment of clinical impact coupled with serological profiling would provide enhanced understanding of the local and systemic impact mediated by metformin. Through correlation of molecular profiles with phenotypic expression changes, as proposed herein, investigators will enhance understanding of the regenerative impact of metformin and the basis for clinical improvement in the setting of senescence.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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.

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: (MATE) Metformin and Aging Trial in the Elderly: A Pilot and Feasibility Study
Estimated Study Start Date : May 1, 2018
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : April 30, 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Metformin
Metformin 500mg tablet by mouth, every 6 to 8 hours for one year
Drug: Metformin
Oral metformin (up to 2gm) will be given in divided doses
Active Comparator: Placebo
Placebo by mouth every 6 to 8 hours for one year
Drug: Placebo
Oral Placebo will be given in divided doses



Primary Outcome Measures :
  1. Change in frailty [ Time Frame: Baseline, 12 months ]
    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.

  2. Change in balance score standing with feet close together [ Time Frame: Baseline, 12 months ]
    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.

  3. Change in balance score standing in semi tandem position [ Time Frame: Baseline, 12 months ]
    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.

  4. Change in balance score standing in full tandem position [ Time Frame: Baseline, 12 months ]
    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.

  5. Change in gait speed [ Time Frame: Baseline, 12 months ]
    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.

  6. Change in score, standing test from chair [ Time Frame: Baseline,12 months ]
    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.


Secondary Outcome Measures :
  1. Change in Interleukin 6 (pg/ml) [ Time Frame: Baseline, 12 months ]
    Serum will be collected to measure the effect of metformin on senescent markers.

  2. Change in Matrix metalloproteinase (ng/ml) [ Time Frame: Baseline, 12 months ]
    Serum will be collected to measure the effect of metformin on senescent markers.

  3. Change in Plasminogen activator inhibitor [ Time Frame: Baseline, 12 months ]
    Serum will be collected to measure the effect of metformin on senescent markers.

  4. Change in Monocyte chemotactic protein-1 [ Time Frame: Baseline, 12 months ]
    Serum will be collected to measure the effect of metformin on senescent markers.

  5. Change in Activin [ Time Frame: Baseline, 12 months ]
    Serum will be collected to measure the effect of metformin on senescent markers.



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Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03451006


Contacts
Contact: Danielle Jacobson 507-205-7230 Jacobson.Danielle@mayo.edu

Locations
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mandeep Singh, MD, MPH    507-255-5891    singh.mandeep@mayo.edu   
Contact: James Kirkland, MD, PhD    5072933346    kirkland.james@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Mandeep Singh Mayo Clinic

Responsible Party: Mandeep Singh, Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03451006     History of Changes
Other Study ID Numbers: 17-003088
First Posted: March 1, 2018    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to do that

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs