NCT02690285

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1 healthy

Timeline
Completed

Started Mar 2016

Longer than P75 for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2016

Completed
15 days until next milestone

First Posted

Study publicly available on registry

February 24, 2016

Completed
6 days until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2017

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2017

Completed
Last Updated

December 31, 2018

Status Verified

December 1, 2018

Enrollment Period

1.2 years

First QC Date

February 9, 2016

Last Update Submit

December 27, 2018

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

  • GSTZ1 haplotype frequency

    The TagMan-based genotyping technology will be used for GSTZ1 haplotype analysis from both blood and cheek samples. Haplotype variations in GSTZ1 influence the kinetics of chronically administered investigational medication DCA. The coding region of the GSTZ1 gene contains three functionally important non-synonymous single nucleotide polymorphisms (SNPs) that give rise to five major GSTZ1 haplotypes: KRT (Z1A), KGT (Z1B), EGT (Z1C), EGM (Z1D), and KGM (Z1F).

    Baseline Visit

Secondary Outcomes (1)

  • Peak Plasma Concentration (Cmax) of Dichloroacetate (DCA)

    -10, 0, 5, 10, 20, 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 30 hours post dose

Study Arms (2)

Part 1: glutathione transferase zeta 1 (GSTZ1) haplotyping

OTHER

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

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

Interventions

Dichloroacetate (DCA)DRUG

Dichloroacetate (DCA) 25 mg/kg oral solution will be administered daily for 5 days.

Part 2: Dichloroacetate (DCA) Kinetics
GSTZ1 haplotypingOTHER

One teaspoon of blood is collected by standard phlebotomy. Cheek cells are collected by standard brushing. Samples will be analyzed at two independent laboratories to validate methods for GSTZ1 haplotype analysis.

Also known as: Blood collection, Cheek cell collection
Part 1: glutathione transferase zeta 1 (GSTZ1) haplotypingPart 2: Dichloroacetate (DCA) Kinetics

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UF Health: Clinical Research Center

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Interventions

Dichloroacetic AcidBlood Specimen Collection

Intervention Hierarchy (Ancestors)

ChloroacetatesAcetatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydrocarbons, ChlorinatedHydrocarbons, HalogenatedHydrocarbonsSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Peter W Stacpoole, PhD, MD

    University of Florida

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
SCREENING
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 9, 2016

First Posted

February 24, 2016

Study Start

March 1, 2016

Primary Completion

May 30, 2017

Study Completion

November 1, 2017

Last Updated

December 31, 2018

Record last verified: 2018-12

Data Sharing

IPD Sharing
Will not share

Locations

US(1)