Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension

NCT03617458 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 180198
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the impact of two interventions against insulin resistance on the composite endpoint of 10% improvement in baseline six minute walk distance or improvement in World Health Organization (WHO) functional class in humans with pulmonary artery hypertension (PAH).

Conditions

Pulmonary Artery Hypertension

Keywords

PAH

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Six Minute Walk Distance (Meters)

  The change in meters walked for the six-minute walk distance from baseline to week 12

  baseline and 12 weeks

• Change From Baseline to Week 12 in World Health Organization Functional Class (WHO FC)

  Change from baseline in WHO functional class at week 12. The World Health Organization (WHO) functional class system was created to define the severity of an individual's symptoms and how they impact on day-to-day activities. The columns represent the randomization assignment and the rows represent if a change in WHO functional class occurred by the participant from baseline to week 12.

  baseline and 12 weeks

Secondary Outcomes (37)

• Change From Baseline to Week 12 in Body Weight (Kilograms)

  baseline and end of 12 weeks

• Change From Baseline to Week 12 in Body Mass Index (BMI)

  baseline and end of 12 weeks

• Change From Baseline to Week 12 in Absolute Six-Minute Walk Distance (Meters)

  baseline and end of 12 weeks

• Change From Baseline to Week 12 in Borg Dyspnea Score

  baseline and end of 12 weeks

• Change From Baseline to Week 12 in Emphasis-10 Quality of Life Survey Score

  baseline and end of 12 weeks

Study Arms (4)

Metformin + mHealth Intervention

ACTIVE COMPARATOR

Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total).

Drug: Metformin; Device: mHealth Intervention

Placebo + Usual Care

PLACEBO COMPARATOR

Patient will receive non active medicine and routine medical care.

Drug: Placebo; Device: Usual Care

Metformin + Usual Care

ACTIVE COMPARATOR

Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total).

Drug: Metformin; Device: Usual Care

Placebo + mHealth Intervention

PLACEBO COMPARATOR

Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue.

Drug: Placebo; Device: mHealth Intervention

Interventions

Metformin DRUG

Metformin is a drug has been on the market for several decades and is considered first line therapy for diabetes mellitus type 2.

Metformin + Usual Care; Metformin + mHealth Intervention

Placebo DRUG

A treatment with no active ingredients or therapeutic effect.

Placebo + Usual Care; Placebo + mHealth Intervention

mHealth Intervention DEVICE

Our Health Insurance Portability and Accountability Act (HIPAA) compliant texting platform is linked to the Fitbit Application Program Interface. Real time activity data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.Subjects assigned to the texting arm will receive 3 texts/day in sync with their preferred morning, lunch, and evening leisure schedule, which is defined at enrollment. These texts will use personal, disease-specific, and provider information to deliver 2 types of messages customized to the current step count and sent in equal proportion. Messages are designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue.

Metformin + mHealth Intervention; Placebo + mHealth Intervention

Usual Care DEVICE

Our HIPAA data will be transmitted from the subject's smartphone to our mHealth platform via cellular network.

Metformin + Usual Care; Placebo + Usual Care

Eligibility Criteria

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

You may qualify if:

• Diagnosed with idiopathic, heritable, or drug- or toxin-associated pulmonary arterial hypertension (PAH) according to World Health Organization consensus recommendations.
• Stable PAH-specific medication regimen for three months prior to enrollment. Subjects with only a single diuretic adjustment in the prior three months will be included. Adjustments in IV prostacyclin for side effect management are allowed.
• Subjects must own a Bluetooth capable modern smartphone capable of receiving and sending text messages and an active data plan.
• WHO Functional Class I-III
• Ambulatory

You may not qualify if:

• Prohibited from normal activity due to wheelchair bound status, bed bound status, reliance on a cane/walker, activity-limiting angina, activity-limiting osteoarthritis, or other condition that limits activity
• Pregnancy
• Diagnosis of PAH etiology other than idiopathic, heritable, or associated with drugs or toxins
• FEV1\> or = 65% predicted AND normal chest imaging
• WHO Functional class IV heart failure
• Requirement of \> 1 diuretic adjustment in the prior 30 days
• Preferred form of activity is not measured by an activity tracker (swimming, ice skating, stair master, or activities on wheels such as bicycling or rollerblading)
• Type I diabetes mellitus
• Prior diagnosis of cirrhosis
• Untreated hypo- or hyper-thyroidism
• estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) \<60 milliliters per minute (mL/min)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Mayo Clinic: collaborator
• The Cleveland Clinic: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991 Sep 1;115(5):343-9. doi: 10.7326/0003-4819-115-5-343.

  PMID: 1863023 BACKGROUND

• Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012 Aug;142(2):448-456. doi: 10.1378/chest.11-1460.

  PMID: 22281797 BACKGROUND

• Mathai SC, Puhan MA, Lam D, Wise RA. The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012 Sep 1;186(5):428-33. doi: 10.1164/rccm.201203-0480OC. Epub 2012 Jun 21.

  PMID: 22723290 BACKGROUND

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension

Interventions

Metformin

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Research Programs Manager
• Organization: Vanderbilt University Medical Center

ph_research@vumc.org

615-322-4703

Study Officials

• Anna R Hemnes, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigators propose a phase II, 2x2 factorial randomized, blinded trial testing metformin versus placebo and a mobile health intervention (mHealth) versus usual care of 12 weeks.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a phase II, 2x2 factorial randomized, blinded trial testing metformin versus placebo and a mHealth intervention (mHealth) versus usual care of 12 weeks.

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: August 6, 2018
• Study Start: August 23, 2018
• Primary Completion: September 9, 2023
• Study Completion: August 19, 2025
• Last Updated: September 22, 2025
• Results First Posted: October 16, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)