Dichloroacetate (DCA) for the Treatment of Pulmonary Arterial Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01083524
• Date of registration: 08/03/2010
• Prospective Registration: No
• Primary sponsor: University of Alberta
• Public title: Dichloroacetate (DCA) for the Treatment of Pulmonary Arterial Hypertension
• Scientific title: A Phase I, Open-Label, Two Centre Study to Evaluate Dichloroacetate(DCA) in Advanced Pulmonary Arterial Hypertension.
• Date of first enrolment: March 2010
• Target sample size: 30
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01083524
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Canada, United Kingdom

Contacts

• Name: Evangelos D. Michelakis, MD
• Affiliation: University of Alberta

• Name: Martin R Wilkins, MD
• Affiliation: Imperial College London

Key inclusion & exclusion criteria

Inclusion Criteria:

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension (Idiopathic, Familial or Anorexigen-associated)

Intervention(s)

Drug: Dichloroacetate Sodium

Primary Outcome(s)

Assessment of safety and tolerability of DCA in patients with pulmonary arterial hypertension. [Time Frame: December 2010]

Secondary Outcome(s)

Changes in Right Ventricular size/function (measured by MRI), biomarkers (NT-proBNP), lung/RV metabolism (measured by FDG-PET) [Time Frame: December 2010]

Functional capacity: change from baseline in Functional Class and 6 min walk [Time Frame: December 2010]

The change in pulmonary vascular resistance from baseline at 16 weeks, measured by cardiac catheterization; [Time Frame: December 2010]

Secondary ID(s)

DCA 20001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Imperial College London