NCT01884051

Brief Summary

Our hypothesis is that optimal treatment of the dysfunctional metabolic pathways which underlie PAH will improve pulmonary vascular function and consequences of the disease.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,899

participants targeted

Target at P75+ for all trials

Timeline
74mo left

Started Sep 2012

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress69%
Sep 2012Jul 2032

Study Start

First participant enrolled

September 1, 2012

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

January 15, 2013

Completed
5 months until next milestone

First Posted

Study publicly available on registry

June 21, 2013

Completed
19 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2032

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2032

Last Updated

September 16, 2025

Status Verified

September 1, 2025

Enrollment Period

19.8 years

First QC Date

January 15, 2013

Last Update Submit

September 15, 2025

Conditions

Idiopathic Pulmonary Arterial HypertensionHeritable Pulmonary Arterial HypertensionScleroderma Associated Pulmonary Arterial HypertensionAppetite Suppressant Associate PAH

Keywords

Pulmonary arterial hypertension

Outcome Measures

Primary Outcomes (4)

  • Ratio of sex hormone metabolites

    The primary outcome measure is the ratio of 2-hydroxyestrogens to 16-hydroxyestrogens among patients compared to both controls and at risk but well subjects.

    5 years

  • Evaluation of insulin resistance in pulmonary arterial hypertension patients/Clinical trial of Metformin in Pulmonary Arterial Hypertension

    We will assess various measures of insulin resistance among patients, compared to healthy control subjects as well as at risk but well subjects. The primary measure will be assessed using the glucose clamp technique to quantify insulin secretion and resistance.

    5 years

  • Mechanism, safety, and efficacy of ACE-2 (Angiotensin Converting Enzyme 2) in the treatment of PAH.

    We will assess the safety and efficacy of ACE-2 for the treatment of established PAH. The primary objective of the study is to determine safety of rhACE2 when administered as a single dose or multiple doses intravenously to subjects with PAH receiving background PAH-specific therapy.

    5 years

  • Clinical Trial of Metformin in Pulmonary Arterial Hypertension

    Specific Aim 1. To test the hypothesis that metformin will ameliorate oxidant stress in pulmonary arterial hypertension Primary safety endpoint: absence of lactic acidosis, withdrawal from the study if attributed to metformin Primary efficacy endpoint: change in urinary and plasma oxidant stress measures (F2 isoprostanes and metabolites, isofurans, and nitrotyrosine) Specific Aim 2. To test the hypothesis that metformin will decrease myocardial lipid content, increase oxidative metabolism and decrease glucose uptake. Primary Endpoints: change in myocardial percent triglycerides (%TGs), kmono/RPP of C11 acetate, and uptake of FDG before and after metformin.

    3 years

Secondary Outcomes (2)

  • Mechanism, safety, and efficacy of ACE-2 in the treatment of PAH.

    5-year

  • Clinical Trial of Metformin in Pulmonary Arterial Hypertension

    3 years

Study Arms (2)

PAH patients

Patients diagnosed with WHO Group 1 PAH

Healthy subjects

Subjects who have been evaluated for heart and lung disease and found to be healthy

Eligibility Criteria

AgeUp to 90 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Cohort 1 subjects will be recruited from our adult and pediatric pulmonary vascular disease clinics. Cohort 2-healthy controls will be recruited form patients families and the general public in middle Tennesssee.

You may qualify if:

  • Project 1
  • Diagnosis of IPAH (idiopathic pulmonary arterial hypertension), HPAH (heritable pulmonary arterial hypertension), or APAH (associated pulmonary arterial hypertension), family members of affected persons
  • Age 0-90, age 12-90 for skin biopsy

You may not qualify if:

  • Other diagnosis
  • Age greater than 90, age less than 12 or greater than 90 for skin biopsy
  • Project 2
  • Diagnosis of IPAH, HPAH, or APAH, family members of affected persons
  • Subjects with reasonably easy access to clinic for blood collection and other testing
  • Subject able to tolerate fasting state prior to sample collection and EndoPAT (endothelial function assessment) testing
  • Other diagnosis
  • Subjects with difficulty reaching clinic for blood collection and other testing
  • Subjects unable to tolerate fasting state
  • Project 3
  • Diagnosis of IPAH, HPAH, or APAH, family members of affected persons
  • Other diagnosis
  • Age less than 7 or greater than 90

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Related Publications (8)

  • Austin ED, Cogan JD, West JD, Hedges LK, Hamid R, Dawson EP, Wheeler LA, Parl FF, Loyd JE, Phillips JA 3rd. Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females. Eur Respir J. 2009 Nov;34(5):1093-9. doi: 10.1183/09031936.00010409. Epub 2009 Apr 8.

    PMID: 19357154BACKGROUND

  • Robbins IM, Newman JH, Johnson RF, Hemnes AR, Fremont RD, Piana RN, Zhao DX, Byrne DW. Association of the metabolic syndrome with pulmonary venous hypertension. Chest. 2009 Jul;136(1):31-36. doi: 10.1378/chest.08-2008. Epub 2009 Feb 2.

    PMID: 19188551BACKGROUND

  • Ferreira AJ, Shenoy V, Yamazato Y, Sriramula S, Francis J, Yuan L, Castellano RK, Ostrov DA, Oh SP, Katovich MJ, Raizada MK. Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med. 2009 Jun 1;179(11):1048-54. doi: 10.1164/rccm.200811-1678OC. Epub 2009 Feb 26.

    PMID: 19246717BACKGROUND

  • Pugh ME, Robbins IM, Rice TW, West J, Newman JH, Hemnes AR. Unrecognized glucose intolerance is common in pulmonary arterial hypertension. J Heart Lung Transplant. 2011 Aug;30(8):904-11. doi: 10.1016/j.healun.2011.02.016. Epub 2011 Apr 13.

    PMID: 21493097BACKGROUND

  • West J. Cross talk between Smad, MAPK, and actin in the etiology of pulmonary arterial hypertension. Adv Exp Med Biol. 2010;661:265-78. doi: 10.1007/978-1-60761-500-2_17.

    PMID: 20204736BACKGROUND

  • Brittain EL, Niswender K, Agrawal V, Chen X, Fan R, Pugh ME, Rice TW, Robbins IM, Song H, Thompson C, Ye F, Yu C, Zhu H, West J, Newman JH, Hemnes AR. Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension. J Am Heart Assoc. 2020 Nov 17;9(22):e018349. doi: 10.1161/JAHA.120.018349. Epub 2020 Nov 10.

    PMID: 33167773DERIVED

  • Hemnes AR, Rathinasabapathy A, Austin EA, Brittain EL, Carrier EJ, Chen X, Fessel JP, Fike CD, Fong P, Fortune N, Gerszten RE, Johnson JA, Kaplowitz M, Newman JH, Piana R, Pugh ME, Rice TW, Robbins IM, Wheeler L, Yu C, Loyd JE, West J. A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension. Eur Respir J. 2018 Jun 21;51(6):1702638. doi: 10.1183/13993003.02638-2017. Print 2018 Jun.

    PMID: 29903860DERIVED

  • Shenoy V, Kwon KC, Rathinasabapathy A, Lin S, Jin G, Song C, Shil P, Nair A, Qi Y, Li Q, Francis J, Katovich MJ, Daniell H, Raizada MK. Oral delivery of Angiotensin-converting enzyme 2 and Angiotensin-(1-7) bioencapsulated in plant cells attenuates pulmonary hypertension. Hypertension. 2014 Dec;64(6):1248-59. doi: 10.1161/HYPERTENSIONAHA.114.03871. Epub 2014 Sep 15.

    PMID: 25225206DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

We plan to collect the following samples on all subjects: DNA, RNA, white cells, plasma, serum, urine We plan to collect the following samples on selected subjects: Skin biopsy

MeSH Terms

Conditions

Familial Primary Pulmonary HypertensionPulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, PulmonaryLung DiseasesRespiratory Tract Diseases

Study Officials

  • James E Loyd, MD

    Vanderbilt University Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly L Fox

CONTACT

800-288-0378Kelly.Burke@vumc.org

Shannon Cordell, BSN

CONTACT

615-343-8277shannon.eason@vumc.org

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

January 15, 2013

First Posted

June 21, 2013

Study Start

September 1, 2012

Primary Completion (Estimated)

July 1, 2032

Study Completion (Estimated)

July 1, 2032

Last Updated

September 16, 2025

Record last verified: 2025-09

Locations

US(1)