Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension

NCT04908397 | Completed Phase 1 Results

• 1 other identifier: 210899
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In preparation for a future mechanistic study, investigators now propose to test the specific hypothesis that carnitine consumption is not reduced in PAH, that plasma carnitine levels are stable over time in PAH and that carnitine supplementation in PAH can increase plasma carnitine and thereby delivery of carnitine to the RV and possibly improve RV function. Investigators propose three aims in humans to test this mechanistic hypothesis, 1) Measure the oral consumption of carnitine in human PAH. This aim will use food diaries and carnitine supplement use questionnaires in PAH patients to test the hypothesis that carnitine supplementation is uncommon in PAH and food consumption is adequate. Aim 2) Measure the stability over time in plasma carnitine levels in PAH patients. This aim will test the hypothesis that plasma carnitine is not affected by disease severity and is stable over time in PAH patients. Investigators will measure plasma carnitine concentration and markers of fatty acid oxidation at Visit 1 and Visit 2. 3) Perform a mechanistic pilot study using carnitine supplementation to enhance circulating carnitine in PAH. This small pilot study will test the hypothesis that carnitine supplementation increases plasma carnitine (primary endpoint) and will test for physiologic effects using six minute walk testing, echocardiography and plasma markers of lipid metabolism.

Conditions

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Primary Pulmonary Hypertension; Lung Diseases; Carnitine Nutritional Deficiency

Outcome Measures

Primary Outcomes (1)

• Plasma Carnitine Concentration

  Change in plasma Carnitine concentration from Visit 2 (Week 12) to Visit 4 (Week 14).

  2 weeks of intervention

Secondary Outcomes (7)

• Prevalence of Carnitine Supplement Use

  12 weeks

• Carnitine Ingestion Use Through Food

  Reported week 1 (3 days leading up to visit 1) and week 12 (3 days leading up to visit 2).

• Six-minute Walk

  14 weeks

• WHO Functional Class

  14 weeks

• Patient Reported Side Effects

  2 weeks- between visit 2 and visit 4

Study Arms (1)

Supplement

EXPERIMENTAL

Form: 500 mg L-carnitine tablet Dosage: Subjects 50-90kg: 3g/day Subjects \<50kg or \>90kg: 50mg/kg/day Frequency: twice a day for 2 weeks

Dietary Supplement: L-carnitine

Interventions

L-carnitine DIETARY_SUPPLEMENT

supplement provided twice a day for 2 weeks

Also known as: Carnitine, Carnitor

Supplement

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 or older.
• Diagnosed with idiopathic, heritable, simple congenital heart defect, 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.
• FEV1\> or = 60% predicted and no more than mild abnormalities on lung imaging
• WHO Functional Class II-IV
• 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, simple congenital heart defect, or associated with drugs or toxins
• Drug and toxin associated PAH patients with active drug use
• Prior diagnosis of cirrhosis
• Malignancy
• eGFR by MDRD \<60mL/min
• Known allergy to l-carnitine supplements

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Lung Diseases

Interventions

Carnitine

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals

Results Point of Contact

• Title: Anna R. Hemnes
• Organization: Vanderbilt University Medical Center

anna.r.hemnes@vumc.org

615-343-8227

Study Officials

• Anna R Hemnes

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Allergy, Pulmonary, and Critical Care Medicine

Model Details: This is a single-center, prospective study enrolling 10 PAH patients. All eligible participants will be given carnitine supplements for 2 weeks.

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: June 1, 2021
• Study Start: September 29, 2021
• Primary Completion: June 1, 2023
• Study Completion: June 30, 2023
• Last Updated: September 30, 2025
• Results First Posted: February 13, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 2 years after study completion.
• Access Criteria: * detailed written description of the project for which the data would be used * acknowledge in any publication resulting from the data, the source of the data, crediting the program support * agree to submit all papers or reports submitted for publication to the PI for review prior to submission

Locations

US (1)