Investigating Senolytic Properties in Pulmonary Rehabilitation and Metformin in COPD Exacerbations (INSPIRE-COPD-E)

The purpose of this study is to investigate the safety and tolerability of Metformin and how it changes blood markers associated with aging in persons who have chronic obstructive pulmonary disease (COPD) who do not have diabetes.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Christopher Mosher, MD; Phone Number: (919) 684-8111; Email: christopher.mosher@duke.edu
• Study Contact Backup: Name: Jessica Shier; Phone Number: (919) 684-9139; Email: jessica.shier@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Asthma, Allergy, and Airway Center
      • Contact: Jessica Shier; Phone Number: 919-684-9139; Email: jessica.shier@duke.edu
      • Principal Investigator: Christopher Mosher, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 65 and older
• History of COPD defined by spirometry demonstrating FEV1/FVC < 70%
• 10 or more tobacco pack year history
• History of frequent exacerbations defined as: 1 severe (i.e., COPD hospitalization) or 2 moderate (i.e., outpatient treated exacerbations) in the previous 12 months

Exclusion Criteria:

• Diabetes or actively being treated with metformin
• Metformin allergy
• History of lactic acidosis not explained by acute, severe illness
• History of low vitamin B12 levels and unwilling to begin standard of care treatment for low vitamin B12 levels
• Hepatic impairment defined as history of cirrhosis or abnormal liver function tests (e.g., alanine transaminase (ALT): 7-55 units per liter (U/L), aspartate transaminase (AST): 8-48 U/L, alkaline phosphatase (ALP): 40-129 U/L, or bilirubin: 0.1-1.2 milligrams per deciliter (mg/dL))
• Renal impairment defined as eGFR < 60 mL/min/1.73m2
• Cognitive impairment
• Dementia
• Heart failure with reduced ejection fraction < 50%
• Alcohol use disorder
• Disability preventing in-person visits
• Persons with an unstable medical condition (including but not limited to unstable angina, acute heart failure exacerbation, acute neurological symptoms) or COPD exacerbation within 30 days prior to enrollment will be excluded
• Active treatment with Carbonic Anhydrase Inhibitors including but not limited to topiramate, zonisamide, acetazolamide, diclofenamide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin; Metformin in COPD patients without diabetes	Drug: Metformin; All enrolled participants will receive open-label Metformin for a treatment period of 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine feasibility of metformin administration in older persons with COPD without diabetes	Enroll and retain ≥ 30 (66%) participants through 6 months study period	6 months
Determine acceptability of metformin administration in older persons with COPD without diabetes	≥70% completion of daily symptom diaries & weekly adherence logs	6 months
Determine safety of metformin administration in older persons with COPD without diabetes	≥90% of the blood glucose levels, renal and hepatic function will be within normal limits*; All lactate levels will be normal	6 months
Determine tolerability of metformin administration in older persons with COPD without diabetes	Adverse events and Serious adverse events	6 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Christopher Mosher, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): October 2, 2029

Study Registration Dates

• First Submitted: November 28, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: COPD; COPD Exacerbation
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Organic Chemicals; Biguanides; Guanidines; Amidines; Metformin
• Other Study ID Numbers: Pro00116416; 1K76AG095138-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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