Single-Center Randomized Controlled Phase II Study of Safety and Efficacy of FK-506 (Tacrolimus) in Pulmonary Arterial Hypertension

Mutations in bone morphogenetic protein receptor 2 (BMPR2) are present in >80% of familial and ~20% of sporadic pulmonary arterial hypertension (PAH) patients. Furthermore dysfunctional BMP signaling is a general feature of pulmonary hypertension even in non-familial PAH. We therefore hypothesized that increasing BMP signaling might prevent and reverse the disease. We screened > 3500 FDA approved drugs for their propensity to increase BMP signaling and found FK506 (Tacrolimus) to be a strong activator of BMP signaling. Tacrolimus restored normal function of pulmonary artery endothelial cells, prevented and reversed experimental PAH in mice and rats. Given that Tacrolimus is already FDA approved with a known side-effect profile, it is an ideal candidate drug to use in patients with pulmonary arterial hypertension. The aims of our trial are: 1. Establish the Safety of FK506 in patients with PAH. 2. Evaluate the Efficacy of FK506 in PAH 3. Identify ideal candidates for future FK506 phase III clinical trial.

Stanford is now accepting new patients for this trial. Please contact Edda Spiekerkoetter, MD at 650-724-1493 for more information.



  • drug : Placebo
  • drug : FK506 level 3-5 ng/ml
  • drug : FK506 level 2-3 ng/ml
  • drug : FK506 level < 2 ng/ml

Phase: Phase 2


Ages Eligible For Study:

18 Years - 70 Years

Inclusion Criteria

1. Age ? 18 and < 70 years 2. Diagnosis of WHO Group I Pulmonary Arterial Hypertension (PAH) (Idiopathic (I)PAH, Heritable PAH (including Hereditary Hemorrhagic Telangiectasia), Associated (A)PAH (including collagen vascular disorders, drugs+toxins exposure, congenital heart disease, and portopulmonary disease). 3. Stable on active PAH treatment including any prostacycline or phosphodiesterase inhibitors and the endothelin antagonist Ambrisentan alone or in combination (stability defined as: <10% change in 6MWD, no change in NYHA class, no hospitalization or addition of PAH therapy for at least 3 months). 4. Previous Right Heart Catheterization that documented: 1. Mean PAP ? 25 mmHg. 2. Pulmonary capillary wedge pressure < 15 mmHg. 3. Pulmonary Vascular Resistance ? 3.0 Wood units or 240 dynes/sec/cm5 5. WHO functional class I to IV as judged by the investigator.

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Contact information

Primary Contact:

Edda Spiekerkoetter, MD 650-724-1493

Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305

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