Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

• Adults aged 18 or older.
  • - 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.

Exclusion Criteria:

  • - 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)

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03617458
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Vanderbilt University Medical Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Anna R Hemnes, MD
Principal Investigator Affiliation Vanderbilt University Medical Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Active, not recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pulmonary Artery Hypertension
Additional Details

The investigators propose to test the hypothesis that interventions to improve insulin resistance will improve exercise capacity and World Health Organization (WHO) functional class in PAH. The investigators propose three specific aims to test this 1) A prospective 2x2 factorial design 12-week clinical trial of metformin or placebo and activity intervention or usual care to assess effect on six minute walk and WHO functional class, 2) Assessment of the interventions in Aim 1 in a subset of patients on right ventricle (RV) and peripheral muscle function and lipid content and markers of pulmonary vascular disease to define how these interventions may work in PAH and 3) Identify and prospectively test peripheral blood markers of metformin response in PAH. The broad goals of this work are to demonstrate the efficacy and mechanisms of interventions against insulin resistance in PAH and to identify which patients are most likely to benefit from these interventions, moving to precision medicine in PAH. The investigators are planning a factorial design trial. Patients will be randomized twice. The first is metformin or placebo and is quadruple randomized. The second is mobile health (mHealth) intervention via texts or standard of care and is not blinded to the patients, but is to the investigator and thus is triple randomized.

Arms & Interventions

Arms

Active Comparator: Metformin + mHealth Intervention

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 po three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total).

Placebo Comparator: Placebo + Usual Care

Patient will receive non active medicine and routine medical care.

Active Comparator: Metformin + Usual Care

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).

Placebo Comparator: Placebo + mHealth Intervention

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.

Interventions

Drug: - Metformin

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

Drug: - Placebo

A treatment with no active ingredients or therapeutic effect.

Device: - mHealth Intervention

Our Health Insurance Portability and Accountability Act (HIPPA) 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.

Device: - Usual Care

Our HIPPA 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.

Contact a Trial Team

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Vanderbilt University Medical Center, Nashville, Tennessee

Status

Address

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

For more information, please contact PHA at Research@PHAssociation.org and refer to the terms of service below.

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