Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Change From Baseline in Six Minute Walk Distance (Meters)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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 by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total).
干预措施: Metformin (Drug)
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 by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total).
干预措施: mHealth Intervention (Device)
Placebo + Usual Care
Patient will receive non active medicine and routine medical care.
干预措施: Placebo (Drug)
Placebo + Usual Care
Patient will receive non active medicine and routine medical care.
干预措施: Usual Care (Device)
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).
干预措施: Metformin (Drug)
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).
干预措施: Usual Care (Device)
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.
干预措施: Placebo (Drug)
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.
干预措施: mHealth Intervention (Device)
结局指标
主要结局
Change From Baseline in Six Minute Walk Distance (Meters)
时间窗: baseline and 12 weeks
The change in meters walked for the six-minute walk distance from baseline to week 12
Change From Baseline to Week 12 in World Health Organization Functional Class (WHO FC)
时间窗: baseline and 12 weeks
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.
次要结局
- 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)
- Change From Baseline to Week 12 in Daily Step Count, as Measured by the Mean Daily Step Count(baseline and end of 12 weeks)
- 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(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Daily Aerobic Time (Minutes)(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Total Daily Activity Assessed in Step Counts Per Minute(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Resting Heart Rate (Beats Per Minute)(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Homeostatic Model Assessment (HOMA)-Insulin Resistance (IR)(baseline and end of 12 weeks)
- Number of Participants With Abnormal Laboratory Values of Plasma Estradiol Metabolites(baseline and end of 12 weeks)
- Number of Participants With Abnormal Laboratory Values of Urine Estradiol Metabolites(baseline and end of 12 weeks)
- Number of Participants With Abnormal Laboratory Values of Plasma Lipid Profile(baseline and end of 12 weeks)
- Number of Participants With Abnormal Laboratory Values of Plasma Free Fatty Acid Profiles(baseline and end of 12 weeks)
- Number of Participants With Abnormal Laboratory Values of Plasma Acylcarnitine Profiles(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Plasma Brain Natriuretic Peptide (BNP) Laboratory Value Measured in pg/ml(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Quadriceps Skeletal Muscle Triglyceride Content, as Measured by % Triglycerides(baseline and end of 12 weeks)
- 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(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Quadriceps Skeletal Muscle Strength During the Muscle Strength and Function Test, as Measured by Maximum Contraction Strength(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Quadriceps Skeletal Muscle Contractile Tissue Cross-sectional(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in RV Myocardial Muscle Triglyceride Content, as Measured by % Triglycerides(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Tricuspid Annular Plane Systolic Excursion (TAPSE), Expressed in mm.(baseline and end of 12 weeks)
- Change From Baseline in Right Ventricle (RV) and Left Ventricle (LV) Ejection Fraction Values as Assessed by Echocardiogram Results, Expressed in Percentage (%).(baseline and end of 12 weeks)
- Change From Baseline in Right Ventricle (RV) Fractional Area, as Assessed by Echocardiogram Results, Expressed in Percentage (%).(baseline and end of 12 weeks)
- Change From Baseline in Tricuspid Annular Velocity (S'), as Assessed by Echocardiogram Results, Expressed in cm/Sec(baseline and end of 12 weeks)
- Change From Baseline in Tricuspid Regurgitant (TR) Velocity, as Assessed by Echocardiogram Results, Expressed in m/Sec.(baseline and end of 12 weeks)
- Change From Baseline in Estimated Right Ventricle (RV) and Right Atrial (RA) Pressure, as Assessed by Echocardiogram Results, Expressed in mmHg(baseline and end of 12 weeks)
- Change From Baseline in Right Ventricle (RV) and Left Ventricle (LV) Diastolic Function as Assessed by Doppler Inflow Patterns on Echocardiogram.(baseline and end of 12 weeks)
- Change From Baseline in Right Ventricle (RV) Free Wall Longitudinal Strain, as Assessed by Echocardiogram Results, and Expressed as Percent (%) Change in Myocardial Deformation.(baseline and end of 12 weeks)
- Number of Participants With a Change in Screening Clinical Characteristics(baseline and end of 12 weeks)
- Number of Patients With Treatment - Emergent Adverse Events (Safety and Tolerability of mHealth Intervention and Drug Treatment in PAH Subjects)(baseline and end of 12 weeks)
- Patient Satisfaction of Treatment Interventions, as Measured by Change in Emphasis-10 Survey Score(baseline and end of 12 weeks)
- Dropout Rate Incidence(baseline and end of 12 weeks)
- Number of Patients With a PAH-related Hospitalization Incidence(baseline and end of 12 weeks)
- Change From Baseline to Week 12 in Patient Medication Regimen, as Measured by Percentage (%) of Subjects With a Change in Medication Regimen(baseline and end of 12 weeks)
- Incidence of Death(baseline to/and 12 weeks)
研究者
Anna Hemnes
Associate Professor
Vanderbilt University Medical Center