Phase 1
N=10
Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension · Familial Primary Pulmonary Hypertension · Primary Pulmonary Hypertension · Lung Diseases · Carnitine Nutritional Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT04908397 ↗Enrolled (actual)
10
Serious AEs
10.0%
Results posted
Feb 2025
Primary outcome: Primary: Plasma Carnitine Concentration — 44 uM
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- L-carnitine (Dietary_supplement)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Vanderbilt University Medical Center
- Primary completion
- Jun 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma Carnitine Concentration |
44 | — |
| SECONDARY Prevalence of Carnitine Supplement Use |
0; 0 | — |
| SECONDARY Carnitine Ingestion Use Through Food |
7; 7 | — |
| SECONDARY Six-minute Walk |
13.14286 | — |
| SECONDARY WHO Functional Class |
3; 4; 2; 5 | — |
| SECONDARY Patient Reported Side Effects |
1 | — |
| SECONDARY Echocardiography Measurements of TAPSE and RV Fractional Area |
0.543; -0.086; 0.736; 0.107 | — |
| SECONDARY Stability of Plasma Carnitine |
2.708 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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
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, 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
Data sourced from ClinicalTrials.gov (NCT04908397). 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.