Pyruvate Dehydrogenase Complex DeficiencyPhase 3DCA/PDCDNCT02616484
Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
A Phase 3 study testing Dichloroacetate (DCA) and Genotype in people with Pyruvate Dehydrogenase Complex Deficiency, run by Saol Therapeutics Inc at 10 sites in United States.
Trial summary
The objective of this research study is to conduct a pivotal phase 3 trial of treatment with the investigational drug dichloroacetate (DCA) in young children with deficiency of the pyruvate dehydrogenase complex (PDC). Read more about this study
- Who is it for?
- Ages 6 months to 17 years
- Conditions the study is for
- Pyruvate Dehydrogenase Complex Deficiency
- What is being tested?
- Dichloroacetate (DCA) and Genotype
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 10 sitesUnited States
- Study dates
- 14 Jul 2020to 27 Aug 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 6 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 6 m through 17 y
- Presence of characteristic clinical or metabolic features of pyruvate dehydrogenase complex deficiency (PDCD) and
- Presence of a known pathogenic mutation of a gene that is specifically associated with PDCD.
Who cannot join
- A genetic mitochondrial disease other than those stipulated under inclusion criteria Primary disorders of amino acid metabolism; primary disorders of fatty acid oxidation Secondary lactic acidosis due to impaired oxygenation or circulation (cardiomyopathy or congenital heart defect) Renal insufficiency (defined as: requires chronic dialysis or serum creatinine ≥ 1.2 mg/dl; creatinine clearance <60 ml/min Primary hepatic disease unrelated to PDCD Pregnancy or breast feeding
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
University of Florida
Gainesville, Florida, 32611
Baylor College of Medicine
Houston, Texas, 77030
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 15224
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of Utah
Salt Lake City, Utah, 84113
Seattle Children's Hospital
Seattle, Washington, 98105
Stanford University
Stanford, California, 94305
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
The objective of this research study is to conduct a pivotal phase 3 trial of treatment with the investigational drug dichloroacetate (DCA) in young children with deficiency of the pyruvate dehydrogenase complex (PDC). PDC deficiency (PDCD) is the most common cause of congenital lactic acidosis and is a frequently fatal metabolic disease of childhood for which no proven treatment exists. The investigators predict that DCA represents targeted potential therapy for PDCD because of its ability to increase both the catalytic activity and stability of the enzyme complex. The conclusions of numerous laboratory and clinical investigations are consistent with this postulate and have led to the designation of DCA as an Orphan Product for congenital lactic acidosis by the Food and Drug Administration.
A novel Observer reported outcome (ObsRO) survey that is completed by study participant's parent/caregiver, is the efficacy outcome measure.
Funding Source - FDA OOPD
Read the detailed description
Clinical sites will be established across the United States for study participation. The investigators will conduct a randomized, placebo-controlled, double-blind trial of 24 evaluable children (30 randomized), aged 6 months through 17 years, with confirmed diagnosis of PDC Deficiency.
Study participants complete Screening procedures at Visit 1 to confirm eligibility for study participation. Screening study procedures include medical history review and physical exam; blood and urine collection, and collection of cheek (buccal) cells; training to complete the ObsRO daily survey. The ObsRO is a survey developed for this study to evaluate how study participants are feeling and functioning in the home setting. The ObsRO survey is completed by the study participant parent/caregiver every day during both treatment periods (study medication and placebo) of study participation (approximately 9 months). During treatment period 1 and 2 (4 months of study medication and 5 months of placebo), the study participant will communicate with the study team at least 2 times per month to evaluate the child's level of health, and compliance with daily survey completion and taking the study medication.
Study participants complete Baseline study procedures at Visit 2 prior to randomization to treatment. Baseline study procedures include, medical history review and physical exam; blood and urine collection; 3 day food record. The study medication will be shipped to the study participants home each month of study participation.
Safety labs are completed during each randomization period (month 3 and month 5). The safety labs can be completed at the clinical trial site, or at any standard clinical laboratory.
Study participants will complete a study visit after each randomization period (month 5 and 9) to complete study assessments at the same clinical site. Visit study procedures include medical history review and physical exam; blood and urine collection; 3 day food record.
Study participants who complete both treatment periods and did not sustain serious adverse events attributable to DCA, will be offered continued access to investigational medication DCA through an open-label access program until the study concludes. Study participants must sign a separate consent form for participation in the open-label access phase of this clinical trial and must complete a study visit every 6 months at the same clinical site for study assessments that include medical history review and physical exam, blood and urine collection. The study medication will continue to be mailed to the study participant during the open-label phase at the same dose received during the blinded phase of the study.
Study participants will be stratified according to their predicted rate of DCA metabolism and clearance, based on genotyping prior to randomization (completed at visit 1 buccal cell collection).
Study participants will continue whatever diet and other "standard of care" is deemed appropriate by their local expert clinicians.
- Being tested
- Dichloroacetate (DCA), Placebo, Genotype
- Keywords
- Sodium Dichloroacetate, Treatment of PDCD with Dichloroacetate
- Medical subject headings
- Pyruvate Dehydrogenase Complex Deficiency Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dichloroacetate (DCA)Drug
Also called Sodium Dichloroacetate
Study medication DCA is an oral solution mixed with an artificial sweetener containing aspartame and strawberry extract (50mg/mL)
Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens:
EGT carriers will receive 12 mg/kg/12hr DCA. EGT non-carriers will receive 6 mg/kg/12 hr DCA.
PlaceboOther
Participants will receive the same volume of placebo in liquid form given during DCA treatment arm. Liquid will be an exact replication of DCA formulation with no DCA added.
GenotypeGenetic
Participants will be genotyped to determine GSTZ1 haplotype status.
| Study group | Role | What they receive |
|---|---|---|
| Dichloroacetate, then Placebo | Active comparator | This group will start on the Dichloroacetate (DCA) treatment which will last for 4 months. After 4 months a 1 month washout period will occur. After the 1 month the group will crossover to the placebo treatment for 4 months.
Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens Receives: Drug: Dichloroacetate (DCA); Other: Placebo; Genetic: Genotype |
| Placebo, then Dichloroacetate | Placebo comparator | This group will start on the placebo treatment which will last for 4 months. After 4 months a 1 month washout period will occur. After the 1 month the group will crossover to the Dichloroacetate (DCA) treatment for 4 months.
Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens Receives: Drug: Dichloroacetate (DCA); Other: Placebo; Genetic: Genotype |
What is being measured
The primary outcome is the main question the study is designed to answer.
The efficacy will be measured between the groups by using the Observer Reported Outcome (ObsRO) measure of health.
The efficacy of dichloroacetate will be determined by applying a novel Observer Reported Outcome (ObsRO) measure of health. The ObsRO scores will be graded on a Likert Scale from 0-4. (0 being absent and 4 being extremely severe).
Measured: 9 months
The number of participants with adverse events will be compared between the groups.
This is to evaluate the safety and tolerability of dichloroacetate by comparing the 1) number and 2) severity of adverse events during both the double-blind and open label treatment phases.
Measured: 9 months
Secondary outcomes (3)
Karnofsky/Lansky Performance Status
The Karnofsky/Lansky performance Scale is completed by the study team. It is a measure of the study participants functional ability to carry on activities of daily living.
The Karnofsky Scale is used for study participants age greater than 16 years. The Lansky Scale is used for study participants age less than 16 years.
Measured: 9 months
Blood lactate levels between the groups.
The measurement of blood lactate level will be performed.
Measured: 9 months
Plasma β-hydroxybutyrate (β-OHB) concentrations between the groups.
The measurement of plasma β-hydroxybutyrate (β-OHB) concentrations will be performed.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2015 (estimated)
- Study start14 Jul 2020
- Primary completion27 Aug 2025 (estimated)
- Study completion27 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (36)Papers the sponsor has linked to this study.
- Other trials for Pyruvate Dehydrogenase Complex DeficiencyStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Saol Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medosome Biotec LLC
- Responsible party
- Sponsor
- Investigators
- Richard Neibeger, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02616484
- Sponsor's protocol ID
- IRB201500698 - A - N
- Acronym
- DCA/PDCD
- Status last verified
- May 2025
- First submitted
- 17 Nov 2015
- Last updated
- 4 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012 Jul;106(3):385-94. doi: 10.1016/j.ymgme.2012.03.017.
PubMed 22896851DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS. Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. Mol Genet Metab. 2012 Nov;107(3):394-402. doi: 10.1016/j.ymgme.2012.09.001. Epub 2012 Sep 7.
PubMed 23021068Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N. Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Sci Transl Med. 2013 Mar 6;5(175):175ra31. doi: 10.1126/scitranslmed.3004986.
PubMed 23467562Stacpoole PW. The dichloroacetate dilemma: environmental hazard versus therapeutic goldmine--both or neither? Environ Health Perspect. 2011 Feb;119(2):155-8. doi: 10.1289/ehp.1002554. Epub 2010 Oct 4.
PubMed 20920954Evans OB, Stacpoole PW. Prolonged hypolactatemia and increased total pyruvate dehydrogenase activity by dichloroacetate. Biochem Pharmacol. 1982 Apr 1;31(7):1295-300. doi: 10.1016/0006-2952(82)90019-3.
PubMed 7092922Han Z, Berendzen K, Zhong L, Surolia I, Chouthai N, Zhao W, Maina N, Srivastava A, Stacpoole PW. A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate. Mol Genet Metab. 2008 Apr;93(4):381-7. doi: 10.1016/j.ymgme.2007.10.131. Epub 2008 Feb 21.
PubMed 18206410Ishida N, Kitagawa M, Hatakeyama S, Nakayama K. Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J Biol Chem. 2000 Aug 18;275(33):25146-54. doi: 10.1074/jbc.M001144200.
PubMed 10831586Lu KP, Liou YC, Zhou XZ. Pinning down proline-directed phosphorylation signaling. Trends Cell Biol. 2002 Apr;12(4):164-72. doi: 10.1016/s0962-8924(02)02253-5.
PubMed 11978535Virshup DM, Eide EJ, Forger DB, Gallego M, Harnish EV. Reversible protein phosphorylation regulates circadian rhythms. Cold Spring Harb Symp Quant Biol. 2007;72:413-20. doi: 10.1101/sqb.2007.72.048.
PubMed 18419299Moretto-Zita M, Jin H, Shen Z, Zhao T, Briggs SP, Xu Y. Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13312-7. doi: 10.1073/pnas.1005847107. Epub 2010 Jul 9.
PubMed 20622153Thomas LW, Lam C, Edwards SW. Mcl-1; the molecular regulation of protein function. FEBS Lett. 2010 Jul 16;584(14):2981-9. doi: 10.1016/j.febslet.2010.05.061. Epub 2010 Jun 11.
PubMed 20540941Henderson GH, Whalen PO, Darr RA, Curry SH, Derendorf H, Baumgartner TG, Stacpoole PW: Development of an oral drug formulation for dichloroacetate and thiamine. Drug Devel Indust Pharm, 20:2425-2437, 1994.
Chu PI, Curry SH, Baumgartner TG, Henderson GN, Stacpoole PW. Preparation and stability of intravenous solutions of sodium dichloroacetate (DCA). J Parenter Sci Technol. 1992 Jan-Feb;46(1):16-8.
PubMed 1625103Berendzen K, Theriaque DW, Shuster J, Stacpoole PW. Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency. Mitochondrion. 2006 Jun;6(3):126-35. doi: 10.1016/j.mito.2006.04.001. Epub 2006 May 3.
PubMed 16725381Stacpoole PW, Kerr DS, Barnes C, Bunch ST, Carney PR, Fennell EM, Felitsyn NM, Gilmore RL, Greer M, Henderson GN, Hutson AD, Neiberger RE, O'Brien RG, Perkins LA, Quisling RG, Shroads AL, Shuster JJ, Silverstein JH, Theriaque DW, Valenstein E. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics. 2006 May;117(5):1519-31. doi: 10.1542/peds.2005-1226.
PubMed 16651305
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
- ClinicalTrials.gov ID
- NCT02616484
- Acronym / sponsor ID
- DCA/PDCD / IRB201500698 - A - N
- Keywords
- Sodium Dichloroacetate, Treatment of PDCD with Dichloroacetate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Saol Therapeutics IncIndustry (pharma, biotech, devices)
- Collaborators
- Medosome Biotec LLC
- Study start
- 14 Jul 2020 (actual)
- Primary completion
- 27 Aug 2025 (estimated)
- Study completion
- 27 Aug 2025 (estimated)
- First posted
- 30 Nov 2015 (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 objective of this research study is to conduct a pivotal phase 3 trial of treatment with the investigational drug dichloroacetate (DCA) in young children with deficiency of the pyruvate dehydrogenase complex (PDC). PDC deficiency (PDCD) is the most common cause of congenital lactic acidosis and is a frequently fatal metabolic disease of childhood for which no proven treatment exists. The investigators predict that DCA represents targeted potential therapy for PDCD because of its ability to increase both the catalytic activity and stability of the enzyme complex. The conclusions of numerous laboratory and clinical investigations are consistent with this postulate and have led to the designation of DCA as an Orphan Product for congenital lactic acidosis by the Food and Drug Administration.
A novel Observer reported outcome (ObsRO) survey that is completed by study participant's parent/caregiver, is the efficacy outcome measure.
Funding Source - FDA OOPD
Detailed description
Clinical sites will be established across the United States for study participation. The investigators will conduct a randomized, placebo-controlled, double-blind trial of 24 evaluable children (30 randomized), aged 6 months through 17 years, with confirmed diagnosis of PDC Deficiency.
Study participants complete Screening procedures at Visit 1 to confirm eligibility for study participation. Screening study procedures include medical history review and physical exam; blood and urine collection, and collection of cheek (buccal) cells; training to complete the ObsRO daily survey. The ObsRO is a survey developed for this study to evaluate how study participants are feeling and functioning in the home setting. The ObsRO survey is completed by the study participant parent/caregiver every day during both treatment periods (study medication and placebo) of study participation (approximately 9 months). During treatment period 1 and 2 (4 months of study medication and 5 months of placebo), the study participant will communicate with the study team at least 2 times per month to evaluate the child's level of health, and compliance with daily survey completion and taking the study medication.
Study participants complete Baseline study procedures at Visit 2 prior to randomization to treatment. Baseline study procedures include, medical history review and physical exam; blood and urine collection; 3 day food record. The study medication will be shipped to the study participants home each month of study participation.
Safety labs are completed during each randomization period (month 3 and month 5). The safety labs can be completed at the clinical trial site, or at any standard clinical laboratory.
Study participants will complete a study visit after each randomization period (month 5 and 9) to complete study assessments at the same clinical site. Visit study procedures include medical history review and physical exam; blood and urine collection; 3 day food record.
Study participants who complete both treatment periods and did not sustain serious adverse events attributable to DCA, will be offered continued access to investigational medication DCA through an open-label access program until the study concludes. Study participants must sign a separate consent form for participation in the open-label access phase of this clinical trial and must complete a study visit every 6 months at the same clinical site for study assessments that include medical history review and physical exam, blood and urine collection. The study medication will continue to be mailed to the study participant during the open-label phase at the same dose received during the blinded phase of the study.
Study participants will be stratified according to their predicted rate of DCA metabolism and clearance, based on genotyping prior to randomization (completed at visit 1 buccal cell collection).
Study participants will continue whatever diet and other "standard of care" is deemed appropriate by their local expert clinicians.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dichloroacetate, then Placebo | Active comparator | Drug: Dichloroacetate (DCA), Other: Placebo, Genetic: GenotypeThis group will start on the Dichloroacetate (DCA) treatment which will last for 4 months. After 4 months a 1 month washout period will occur. After the 1 month the group will crossover to the placebo treatment for 4 months. Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens |
| Placebo, then Dichloroacetate | Placebo comparator | Drug: Dichloroacetate (DCA), Other: Placebo, Genetic: GenotypeThis group will start on the placebo treatment which will last for 4 months. After 4 months a 1 month washout period will occur. After the 1 month the group will crossover to the Dichloroacetate (DCA) treatment for 4 months. Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens |
Who may qualify
- Ages
- 6 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Age 6 m through 17 y
- Presence of characteristic clinical or metabolic features of pyruvate dehydrogenase complex deficiency (PDCD) and
- Presence of a known pathogenic mutation of a gene that is specifically associated with PDCD.
Key exclusion criteria (1 listed)
- A genetic mitochondrial disease other than those stipulated under inclusion criteria Primary disorders of amino acid metabolism; primary disorders of fatty acid oxidation Secondary lactic acidosis due to impaired oxygenation or circulation (cardiomyopathy or congenital heart defect) Renal insufficiency (defined as: requires chronic dialysis or serum creatinine ≥ 1.2 mg/dl; creatinine clearance <60 ml/min Primary hepatic disease unrelated to PDCD Pregnancy or breast feeding
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)Also: Sodium DichloroacetateStudy medication DCA is an oral solution mixed with an artificial sweetener containing aspartame and strawberry extract (50mg/mL) Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens: EGT carriers will receive 12 mg/kg/12hr DCA. EGT non-carriers will receive 6 mg/kg/12 hr DCA. | Drug | Dichloroacetate, then Placebo, Placebo, then Dichloroacetate |
| PlaceboParticipants will receive the same volume of placebo in liquid form given during DCA treatment arm. Liquid will be an exact replication of DCA formulation with no DCA added. | Other | Dichloroacetate, then Placebo, Placebo, then Dichloroacetate |
| GenotypeParticipants will be genotyped to determine GSTZ1 haplotype status. | Genetic | Dichloroacetate, then Placebo, Placebo, then Dichloroacetate |
Primary outcome
The efficacy will be measured between the groups by using the Observer Reported Outcome (ObsRO) measure of health.
Time frame: 9 months
The efficacy of dichloroacetate will be determined by applying a novel Observer Reported Outcome (ObsRO) measure of health. The ObsRO scores will be graded on a Likert Scale from 0-4. (0 being absent and 4 being extremely severe).
The number of participants with adverse events will be compared between the groups.
Time frame: 9 months
This is to evaluate the safety and tolerability of dichloroacetate by comparing the 1) number and 2) severity of adverse events during both the double-blind and open label treatment phases.
3 secondary outcomes
Karnofsky/Lansky Performance Status
Time frame: 9 months
Blood lactate levels between the groups.
Time frame: 9 months
Plasma β-hydroxybutyrate (β-OHB) concentrations between the groups.
Time frame: 9 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2025.
- Background: PubMed 22896851Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012 Jul;106(3):385-94. doi: 10.1016/j.ymgme.2012.03.017.
- Background: PubMed 23021068DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS. Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. Mol Genet Metab. 2012 Nov;107(3):394-402. doi: 10.1016/j.ymgme.2012.09.001. Epub 2012 Sep 7.
- Background: PubMed 23467562Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N. Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Sci Transl Med. 2013 Mar 6;5(175):175ra31. doi: 10.1126/scitranslmed.3004986.
- Background: PubMed 20920954Stacpoole PW. The dichloroacetate dilemma: environmental hazard versus therapeutic goldmine--both or neither? Environ Health Perspect. 2011 Feb;119(2):155-8. doi: 10.1289/ehp.1002554. Epub 2010 Oct 4.
- Background: PubMed 7092922Evans OB, Stacpoole PW. Prolonged hypolactatemia and increased total pyruvate dehydrogenase activity by dichloroacetate. Biochem Pharmacol. 1982 Apr 1;31(7):1295-300. doi: 10.1016/0006-2952(82)90019-3.
- Background: PubMed 18206410Han Z, Berendzen K, Zhong L, Surolia I, Chouthai N, Zhao W, Maina N, Srivastava A, Stacpoole PW. A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate. Mol Genet Metab. 2008 Apr;93(4):381-7. doi: 10.1016/j.ymgme.2007.10.131. Epub 2008 Feb 21.
- Background: PubMed 10831586Ishida N, Kitagawa M, Hatakeyama S, Nakayama K. Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J Biol Chem. 2000 Aug 18;275(33):25146-54. doi: 10.1074/jbc.M001144200.
- Background: PubMed 11978535Lu KP, Liou YC, Zhou XZ. Pinning down proline-directed phosphorylation signaling. Trends Cell Biol. 2002 Apr;12(4):164-72. doi: 10.1016/s0962-8924(02)02253-5.
- Background: PubMed 18419299Virshup DM, Eide EJ, Forger DB, Gallego M, Harnish EV. Reversible protein phosphorylation regulates circadian rhythms. Cold Spring Harb Symp Quant Biol. 2007;72:413-20. doi: 10.1101/sqb.2007.72.048.
- Background: PubMed 20622153Moretto-Zita M, Jin H, Shen Z, Zhao T, Briggs SP, Xu Y. Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13312-7. doi: 10.1073/pnas.1005847107. Epub 2010 Jul 9.
- Background: PubMed 20540941Thomas LW, Lam C, Edwards SW. Mcl-1; the molecular regulation of protein function. FEBS Lett. 2010 Jul 16;584(14):2981-9. doi: 10.1016/j.febslet.2010.05.061. Epub 2010 Jun 11.
- BackgroundHenderson GH, Whalen PO, Darr RA, Curry SH, Derendorf H, Baumgartner TG, Stacpoole PW: Development of an oral drug formulation for dichloroacetate and thiamine. Drug Devel Indust Pharm, 20:2425-2437, 1994.
- Individual participant dataSharing planned: No
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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.
Richard Neibeger, MD principal investigator
University of Florida
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dichloroacetate (DCA) and Genotype in people with Pyruvate Dehydrogenase Complex Deficiency, run by Saol Therapeutics Inc at 10 sites 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 3 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
The efficacy will be measured between the groups by using the Observer Reported Outcome (ObsRO) measure of health. (time frame: 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02616484, which also lists 36 linked publications.
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 4 May 2025.