HealthyPhase 1NCT02690285
A Pilot Study of Rapid Haplotyping Procedure for Personalized Dosing of Dichloroacetate (DCA) in Healthy Volunteers
A Phase 1 study testing Dichloroacetate (DCA) and GSTZ1 haplotyping in people with Healthy, run by University of Florida at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Dichloroacetate (DCA) and GSTZ1 haplotyping
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2016to 1 Nov 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy as outline in the physical exam and blood tests
- Non smoker
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
UF Health: Clinical Research Center
Gainesville, Florida, 32610
About this study
Official title: A Pilot Study of Rapid Haplotyping Procedure for Personalized Dosing of Dichloroacetate (DCA) in Healthy Volunteers Part 1: Rapid Haplotyping Procedure for Determining the Response of Patients to DCA. Part 2: Personalized Dosing of Dichloroacetate for the Treatment of Rare and Common Diseases
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.
Read the detailed 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.
- Conditions
- Healthy
- Being tested
- Dichloroacetate (DCA), GSTZ1 haplotyping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dichloroacetate (DCA)Drug
Dichloroacetate (DCA) 25 mg/kg oral solution will be administered daily for 5 days.
GSTZ1 haplotypingOther
Also called Blood collection, Cheek cell collection
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Drug: Dichloroacetate (DCA); Other: GSTZ1 haplotyping |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline Visit
Secondary outcomes (1)
Peak Plasma Concentration (Cmax) of Dichloroacetate (DCA)
After 5 days of oral DCA administration, blood samples will be collected at the specified times for Peak Plasma Concentration (Cmax) analysis.
Measured: -10, 0, 5, 10, 20, 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 30 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study start1 Mar 2016
- Primary completion30 May 2017
- Study completion1 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Medosome Biotec LLC, Food and Drug Administration (FDA)
- Responsible party
- Sponsor
- Investigators
- Peter W Stacpoole, PhD, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02690285
- Sponsor's protocol ID
- IRB201500995 - N
- Other IDs
- R43FD005349, OCR15997
- Status last verified
- Dec 2018
- First submitted
- 9 Feb 2016
- Last updated
- 31 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Rapid Haplotyping Procedure for Personalized Dosing of Dichloroacetate (DCA) in Healthy Volunteers Part 1: Rapid Haplotyping Procedure for Determining the Response of Patients to DCA. Part 2: Personalized Dosing of Dichloroacetate for the Treatment of Rare and Common Diseases
- ClinicalTrials.gov ID
- NCT02690285
- Acronym / sponsor ID
- IRB201500995 - N
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Medosome Biotec LLC, Food and Drug Administration (FDA)
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 30 May 2017 (actual)
- Study completion
- 1 Nov 2017 (actual)
- First posted
- 24 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1: glutathione transferase zeta 1 (GSTZ1) haplotyping | Other | Other: GSTZ1 haplotypingThe participants will have blood collection and cheek cell collection after signing the informed consent, to determine GSTZ1 haplotype. |
| Part 2: Dichloroacetate (DCA) Kinetics | Experimental | Drug: Dichloroacetate (DCA), Other: GSTZ1 haplotypingEight 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). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy as outline in the physical exam and blood tests
- Non smoker
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dichloroacetate (DCA)Dichloroacetate (DCA) 25 mg/kg oral solution will be administered daily for 5 days. | Drug | Part 2: Dichloroacetate (DCA) Kinetics |
| GSTZ1 haplotypingAlso: Blood collection, Cheek cell collectionOne 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. | Other | Part 1: glutathione transferase zeta 1 (GSTZ1) haplotyping, Part 2: Dichloroacetate (DCA) Kinetics |
Primary outcome
GSTZ1 haplotype frequency
Time frame: Baseline Visit
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).
1 secondary outcome
Peak Plasma Concentration (Cmax) of Dichloroacetate (DCA)
Time frame: -10, 0, 5, 10, 20, 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 30 hours post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2018.
- Individual participant dataSharing planned: No
Related trials for Healthy
Recruiting
Trained vs. Untrained: Lower Extremity Pressure Changes
Trained Athletes, Untrained
Not yet recruitingPhase 1
Comparison of Pharmacokinetic/Pharmacodynamic Characteristics and Safety of GZR101-80 Injection With Separately Injected, Simultaneous Doses of GZR33 Injection and Insulin Aspart
Healthy Participants
Active, not recruitingPhase 2
Effect of Equol Supplementation on Arterial Stiffness and Cognition in Healthy Volunteers
Arterial Stiffness, White Matter Lesions
Enrolling by invitationObservational study
Screening for Hematology Branch Protocols
Hematologic Disease and Disorders, Donors
RecruitingPhase 1
A Study of Single and Multiple Subcutaneous or Intravenous Doses of ADX-001 in Healthy Adults to Assess Safety, Effects, and Immune Response
Healthy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter W Stacpoole, PhD, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dichloroacetate (DCA) and GSTZ1 haplotyping in people with Healthy, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GSTZ1 haplotype frequency (time frame: Baseline Visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2018; AzTrials last refreshed its copy on 6 Nov 2026.