DCA for Pyruvate Dehydrogenase Deficiency

(DCA/PDCD Trial)

Not currently recruiting at 10 trial locations

Overseen By Breeana Usher, BS

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Saol Therapeutics Inc

Disqualifiers: Mitochondrial disease, Amino acid disorders, Fatty acid disorders, Renal insufficiency, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called dichloroacetate (DCA) for young children with pyruvate dehydrogenase complex deficiency (PDCD), a rare and serious metabolic disorder. PDCD often leads to high levels of lactic acid in the body, causing various health issues. The study aims to determine if DCA can improve enzyme activity and help manage symptoms. Participants will start with either DCA or a placebo (inactive substance) and switch after a few months. Children diagnosed with PDCD who exhibit specific symptoms related to the condition might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that dichloroacetate (DCA) has been explored as a treatment for various conditions, including pyruvate dehydrogenase complex deficiency (PDCD). Studies have found that DCA can boost the activity of the enzyme complex often lacking in people with this condition. DCA is usually well-tolerated, but like any treatment, it can have side effects.

In earlier research, some patients experienced mild side effects like nausea or an upset stomach. More serious side effects were uncommon but did occur, such as nerve damage and changes in liver function, which researchers carefully monitored during studies. The FDA has recognized DCA as an Orphan Product for treating congenital lactic acidosis, suggesting its potential benefits even though it is not fully approved for PDCD treatment.

Before joining a trial, discussing any concerns with a healthcare provider is advisable. They can help explain the potential risks and benefits based on the latest research findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PDCD?

Unlike the standard treatments for Pyruvate Dehydrogenase Deficiency, which often focus on managing symptoms with dietary changes and supplements, Dichloroacetate (DCA) offers a novel approach by targeting the root cause of the condition. DCA works by activating the enzyme pyruvate dehydrogenase, which plays a critical role in energy production within cells. This mechanism is different because it directly addresses the metabolic dysfunction rather than just alleviating symptoms. Researchers are excited about DCA because it has the potential to improve energy production and overall metabolic function, offering hope for a more effective treatment option for patients.

What evidence suggests that this treatment might be an effective treatment for PDCD?

Research has shown that dichloroacetate (DCA) might help treat pyruvate dehydrogenase complex deficiency (PDCD) by increasing the activity of the malfunctioning enzyme. This boost can lead to improved energy production in cells. Previous patients demonstrated positive results, as DCA enhanced the remaining enzyme activity, improving cellular energy production. In this trial, participants will begin with either DCA treatment or a placebo, followed by a crossover after a washout period. Researchers are studying the drug because it might directly address the main cause of PDCD. While the results are promising, DCA is still under investigation and not yet approved for this condition. Ongoing studies will provide more information about its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Richard Neibeger, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for children aged 6 months to 17 years with Pyruvate Dehydrogenase Complex Deficiency (PDCD), evidenced by a known pathogenic gene mutation and clinical or metabolic features of PDCD. It excludes those with unrelated liver disease, amino acid metabolism disorders, pregnancy, fatty acid oxidation disorders, other genetic mitochondrial diseases besides PDCD, renal insufficiency, or secondary lactic acidosis.

Inclusion Criteria

I have a genetic mutation linked to programmed cell death.

I am between 6 months and 17 years old.

You show signs of pyruvate dehydrogenase complex deficiency (PDCD) in your health or metabolism.

Exclusion Criteria

My condition is not one of the specified mitochondrial diseases.

I have a disorder that affects how my body breaks down fats.

I have high lactic acid levels due to heart issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline study procedures including medical history review, physical exam, and sample collection prior to randomization

1 week

1 visit (in-person)

Treatment Period 1

Participants receive either placebo or dichloroacetate for 4 months, with monthly communication and safety labs

4 months

2 visits (in-person), monthly communication

Washout

1 month washout period between treatment phases

1 month

Treatment Period 2

Participants crossover to the alternate treatment (placebo or dichloroacetate) for 4 months, with monthly communication and safety labs

4 months

2 visits (in-person), monthly communication

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person)

Open-label extension (optional)

Participants may opt into continued access to dichloroacetate with biannual visits for assessments

Long-term

1 visit every 6 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dichloroacetate (DCA)

Trial Overview The study tests Dichloroacetate (DCA) against a placebo in young children with PDCD. DCA could potentially stabilize the enzyme complex affected by this condition. The trial's effectiveness will be measured using an Observer reported outcome survey completed by the child's parent or caregiver.

How Is the Trial Designed?

Group I: Dichloroacetate, then Placebo Active Control 3 Interventions

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

Group II: Placebo, then Dichloroacetate Placebo Group 3 Interventions

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

Dichloroacetate (DCA) is already approved in Canada for the following indications:

Approved in Canada as Dichloroacetic acid for:

• Topical treatment of warts
• Cauterization and removal of skin and tissue lesions

Who Is Running the Clinical Trial?

Saol Therapeutics Inc

Lead Sponsor

Trials

3

Recruited

200+

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Medosome Biotec LLC

Industry Sponsor

Trials

2

Recruited

80+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Chronic administration of dichloroacetate (DCA) for 9.7 to 16.5 years in 8 patients with metabolic deficiencies was generally well-tolerated and effectively maintained normal blood lactate levels, even in children not on strict ketogenic diets.

Despite some modest changes in nerve conduction in a few patients, there were no significant symptoms of peripheral neuropathy, indicating that DCA can be a safe long-term treatment for congenital lactic acidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of dichloroacetate in congenital lactic acidosis. Abdelmalak, M., Lew, A., Ramezani, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02616484

Study Details | NCT02616484 | Trial of Dichloroacetate in ... 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

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16725381/

Therapeutic potential of dichloroacetate for pyruvate ... - PubMed DCA may be particularly effective in children with PDC deficiency by stimulating residual enzyme activity and, consequently, cellular energy metabolism.

3. saolrx.com saolrx.com/saol-therapeutics-announces-enrollment-achievement-in-pivotal-phase-3-trial-for-rare-mitochondrial-disease-pyruvate-dehydrogenase-complex-deficiency-pdcd/

Pyruvate Dehydrogenase Complex Deficiency (PDCD) DCA inhibits PDKs to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. DCA dosing is based on a proprietary ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12419407/

Advances in the therapeutic applications of dichloroacetate as ... Animal studies showed that DCA significantly reduced lens clouding in diabetic rats and dose-dependently improved diabetic cataract formation ...

5. mitoaction.org mitoaction.org/fda-denies-approval-for-dca/

FDA denies approval for dichloroacetate (DCA), a ... FDA denies approval for dichloroacetate (DCA), a treatment for Pyruvate Dehydrogenase Complex Deficiency (PDCD). Emily Grandahl Sep 4, 2025.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06931262

NCT06931262 | Expanded Access Treatment Protocol With ... Expanded Access Treatment Protocol With Dichloroacetate Sodium for Patients With Pyruvate Dehydrogenase Complex Deficiency ... Drug : Dichloroacetate (DCA). Other ...

7. ufhealth.org ufhealth.org/clinical-trials/trial-of-dca-in-pdcd

Trial of DCA in PDCD 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.