Phase 2 N=73 Randomized Triple-blind Treatment

Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension

Pulmonary Artery Hypertension

Bottom Line

View on ClinicalTrials.gov: NCT03617458 ↗

Enrolled (actual)

Serious AEs

13.7%

Results posted

Oct 2024

Primary outcome: Primary: Change From Baseline in Six Minute Walk Distance (Meters) — 414.5; 461.7; 448.9; 483.0 meters

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Metformin (Drug); Placebo (Drug); mHealth Intervention (Device); Usual Care (Device)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Vanderbilt University Medical Center
Primary completion: Sep 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Six Minute Walk Distance (Meters)	414.5; 461.7; 448.9; 483.0; 457.2; 474.9	—
PRIMARY Change From Baseline to Week 12 in World Health Organization Functional Class (WHO FC)	15; 12; 14; 13; 1; 2	—
SECONDARY Change From Baseline to Week 12 in Body Weight (Kilograms)	—	—
SECONDARY Change From Baseline to Week 12 in Body Mass Index (BMI)	—	—
SECONDARY Change From Baseline to Week 12 in Absolute Six-Minute Walk Distance (Meters)	—	—
SECONDARY Change From Baseline to Week 12 in Borg Dyspnea Score	—	—
SECONDARY Change From Baseline to Week 12 in Emphasis-10 Quality of Life Survey Score	—	—
SECONDARY Change From Baseline to Week 12 in Daily Step Count, as Measured by the Mean Daily Step Count	—	—
SECONDARY Change From Baseline to Week 12 in Daily Step Count Goal Attainment, as Measured by the Percentage (%) of Subjects Who Meet Their Daily Step Count Goal	—	—
SECONDARY Change From Baseline to Week 12 in Daily Aerobic Time (Minutes)	—	—
SECONDARY Change From Baseline to Week 12 in Total Daily Activity Assessed in Step Counts Per Minute	—	—
SECONDARY Change From Baseline to Week 12 in Resting Heart Rate (Beats Per Minute)	—	—
SECONDARY Change From Baseline to Week 12 in Homeostatic Model Assessment (HOMA)-Insulin Resistance (IR)	—	—
SECONDARY Number of Participants With Abnormal Laboratory Values of Plasma Estradiol Metabolites	—	—
SECONDARY Number of Participants With Abnormal Laboratory Values of Urine Estradiol Metabolites	—	—
SECONDARY Number of Participants With Abnormal Laboratory Values of Plasma Lipid Profile	—	—
SECONDARY Number of Participants With Abnormal Laboratory Values of Plasma Free Fatty Acid Profiles	—	—
SECONDARY Number of Participants With Abnormal Laboratory Values of Plasma Acylcarnitine Profiles	—	—
SECONDARY Change From Baseline to Week 12 in Plasma Brain Natriuretic Peptide (BNP) Laboratory Value Measured in pg/ml	—	—
SECONDARY Change From Baseline to Week 12 in Quadriceps Skeletal Muscle Triglyceride Content, as Measured by % Triglycerides	—	—
SECONDARY Change From Baseline to Week 12 in Quadriceps Skeletal Muscle Fatigue, as Measured by Total Time to Muscle Fatigue During the Muscle Strength and Function Test	—	—
SECONDARY Change From Baseline to Week 12 in Quadriceps Skeletal Muscle Strength During the Muscle Strength and Function Test, as Measured by Maximum Contraction Strength	—	—
SECONDARY Change From Baseline to Week 12 in Quadriceps Skeletal Muscle Contractile Tissue Cross-sectional	—	—
SECONDARY Change From Baseline to Week 12 in RV Myocardial Muscle Triglyceride Content, as Measured by % Triglycerides	—	—
SECONDARY Change From Baseline to Week 12 in Tricuspid Annular Plane Systolic Excursion (TAPSE), Expressed in mm.	—	—
SECONDARY Change From Baseline in Right Ventricle (RV) and Left Ventricle (LV) Ejection Fraction Values as Assessed by Echocardiogram Results, Expressed in Percentage (%).	—	—
SECONDARY Change From Baseline in Right Ventricle (RV) Fractional Area, as Assessed by Echocardiogram Results, Expressed in Percentage (%).	—	—
SECONDARY Change From Baseline in Tricuspid Annular Velocity (S'), as Assessed by Echocardiogram Results, Expressed in cm/Sec	—	—
SECONDARY Change From Baseline in Tricuspid Regurgitant (TR) Velocity, as Assessed by Echocardiogram Results, Expressed in m/Sec.	—	—
SECONDARY Change From Baseline in Estimated Right Ventricle (RV) and Right Atrial (RA) Pressure, as Assessed by Echocardiogram Results, Expressed in mmHg	—	—
SECONDARY Change From Baseline in Right Ventricle (RV) and Left Ventricle (LV) Diastolic Function as Assessed by Doppler Inflow Patterns on Echocardiogram.	—	—
SECONDARY Change From Baseline in Right Ventricle (RV) Free Wall Longitudinal Strain, as Assessed by Echocardiogram Results, and Expressed as Percent (%) Change in Myocardial Deformation.	—	—
SECONDARY Number of Participants With a Change in Screening Clinical Characteristics	—	—
SECONDARY Number of Patients With Treatment - Emergent Adverse Events (Safety and Tolerability of mHealth Intervention and Drug Treatment in PAH Subjects)	—	—
SECONDARY Patient Satisfaction of Treatment Interventions, as Measured by Change in Emphasis-10 Survey Score	—	—
SECONDARY Dropout Rate Incidence	—	—
SECONDARY Number of Patients With a PAH-related Hospitalization Incidence	—	—
SECONDARY Change From Baseline to Week 12 in Patient Medication Regimen, as Measured by Percentage (%) of Subjects With a Change in Medication Regimen	—	—
SECONDARY Incidence of Death	—	—

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).

Eligibility 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)

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03617458). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.