A Pilot Study of Rapid Haplotyping Procedure for Personalized Dosing of Dichloroacetate (DCA) in Healthy Volunteers

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University of Florida

Status and phase

Phase 1




Other: GSTZ1 haplotyping
Drug: Dichloroacetate (DCA)

Study type


Funder types

Other U.S. Federal agency


OCR15997 (Other Identifier)
IRB201500995 - N

Details and patient eligibility


The purpose of this study is to identify and analyze the frequency of GSTZ1 haplotypes in a healthy adult population and determine the pharmacokinetics of Dichloroacetate (DCA) metabolism based on haplotype analysis. The DCA drug is the first targeted treatment for Pyruvate Dehydrogenase Complex Deficiency (PDCD). This pilot study, focuses on developing a high throughput, sensitive and accurate screening test for determining glutathione transferase zeta 1 (GSTZ1) haplotype status in individuals who would be treated with DCA.

Full description

Pyruvate dehydrogenase complex (PDC) deficiency (PDCD) is a rare disease of mitochondrial energy failure with the life of expectancy of affected children severely truncated. Treatment of PDCD remains a serious, unmet challenge. Dichloroacetate (DCA) represents the first targeted therapy for PDCD by stimulating residual PDC activity. Cumulative experience with DCA has revealed dose accumulation in a subset of the population. This can be abated through personalized dosing of DCA, assigned by haplotype variation in the gene encoding glutathione transferase zeta 1 (GSTZ1), which biotransforms DCA to glyoxylate. Haplotype variations in GSTZ1 influence the kinetics and dynamics of chronically administered DCA. A single dose of DCA has a bioavailability approaching unity and is widely distributed throughout the body. The plasma half-life (t ½) is ~1 hr in drug-naïve subjects. Gender does not influence DCA kinetics or metabolism. The major route of biotransformation is via dehalogenation to glyoxylate by glutathione transferase zeta 1 (GSTZ1). DCA is a mechanism-based inhibitor of GSTZ1, so repeated administration results in increased plasma t ½ and decreased clearance.


45 patients




18 to 70 years old


Accepts Healthy Volunteers

Inclusion criteria

  • Healthy as outline in the physical exam and blood tests
  • Non smoker

Exclusion criteria

  • Cannot comprehend or refuse to sign the informed consent form;
  • Febrile or have other clinical signs of infection;
  • Pregnant or are nursing;
  • In females, cannot or refuse to use contraception or avoid unprotected intercourse during the study;
  • Uncontrolled hypertension (BPs > 160 mmHg or BPd > 100 mmHg) on conventional medication;
  • Anemic (hematocrit < 35% in males; < 35% in females;
  • Serum creatinine ≥ 1.3 mg/dl, TSH > 4.5 mIU/ml; a transaminase (ALT or AST) > 2 x ULN, total bilirubin > 1.2 mg/dl or fasting glucose ≥ 110 mg/dl.
  • History of psychosis, seizures or diabetes mellitus or be receiving anti-psychotic, anti-epileptic or blood glucose-lowering medication.

Trial design

Primary purpose




Interventional model

Single Group Assignment


None (Open label)

45 participants in 2 patient groups

Part 1: glutathione transferase zeta 1 (GSTZ1) haplotyping
Other group
The participants will have blood collection and cheek cell collection after signing the informed consent, to determine GSTZ1 haplotype.
Other: GSTZ1 haplotyping
Part 2: Dichloroacetate (DCA) Kinetics
Experimental group
Eight study participants will be administered oral Dichloroacetate (DCA) 25 mg/kg daily for 5 days. On the fifth day frequent blood samples will be obtain over the following 24 hours. Study participants will complete a DCA kinetic study on day 5, at the Clinical Research Clinic (CRC).
Drug: Dichloroacetate (DCA)
Other: GSTZ1 haplotyping

Trial contacts and locations



Data sourced from clinicaltrials.gov

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