Dichloroacetate (DCA) for the Treatment of Pulmonary Arterial Hypertension

1. Males or females 18 years or older
2. Willing and able to complete informed consent form.

3. Documented diagnosis of PAH:

   • idiopathic, associated with anorexigens or familial;
   • mean pulmonary arterial pressure >25 mm Hg, pulmonary capillary wedge pressure =/\< 15 mm Hg and pulmonary vascular resistance >240 dynes/sec/cm5 (measured by catheter).
4. Receiving stable doses for at least 2 months of one or more medications that are approved for treatment of PAH (endothelin receptor antagonists or phosphodiesterase type 5 inhibitors). Note: Anticoagulant therapy can be adjusted according to target INR and diuretic dose can be adjusted as required.
5. Modified World Health Organization(WHO) classification III-IV; stable for at least 8 weeks prior to enrollment.
6. 6MWD, as performed at screening or within three months (12 weeks) prior to screening, of ≥ 150 meters.
7. Expected survival of > 6 months.
8. ALT or AST levels \< 3 times the upper limit of normal

9. Sexually active subjects must use an acceptable method of contraception while participating in the study, consisting of:

   1. Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner of female subject
   2. Oral contraceptives (either combined or progestogen only) with double-barrier method of contraception consisting of spermicide with either condom or diaphragm. Women of child-bearing potential using an oral contraceptive in combination with a double-barrier method of contraception are required to continue to use this form of contraception for 6 weeks following discontinuation of study medication
   3. Double-barrier method of contraception consisting of spermicide with either condom or diaphragm
   4. IUD with documented failure rate of less than 1% per year
10. Females of childbearing potential must have negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.

Exclusion Criteria:

1. Previous treatment with any formulation of DCA.
2. Known allergy or hypersensitivity to any excipient of DCA.
3. Clinically significant biochemical abnormality.
4. Clinical evidence of pre-existing neuropathy.
5. Use of investigational product or device within 30 days prior to dosing, or known requirement for any investigational agent prior to completion of all scheduled study assessments.
6. Known to be positive for human immunodeficiency virus (HIV).
7. Additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities, including bleeding disorders, arrhythmia, organ transplant, organ failure, current neoplasm, poorly controlled diabetes mellitus, and serious neurological disorders.

8. Blood results (performed within 14 days from study registration) as outlined below:

   • Absolute neutrophil count (ANC)\<1500 cells/mm3.
   • Platelets\<100,000 cells/mm3.
   • Hemoglobin \<10 g/dl. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
   • S-Urea > 25 mg/dl
   • Creatinine clearance ≤ 30 ml
   • Bilirubin > 2.0 mg/dl
   • ALT >3 x normal range
   • AST >3 x normal range
9. Pregnant or lactating at screening, or planning to become pregnant (self or partner) at any time during study.
10. Contraindication to magnetic resonance imaging.
11. Unable to provide informed consent.