Dichloroacetate randomized controlled trial in MELAS

13 evidence topics · 1 source

Objective

Efficacy of dichloroacetate in MELAS

“To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).” (opens the source at this quote in a new tab)
“The authors hypothesized that chronic cerebral lactic acidosis exacerbates neuronal injury in MELAS and therefore, investigated DCA, a potent lactate-lowering agent, as potential treatment for MELAS.” (opens the source at this quote in a new tab)

Location and study date

No evidence found.

Study design

Crossover design

“3-year cross-over trial” (opens the source at this quote in a new tab)

Eligibility criteria

Disease and genotype

“MELAS and the A3243G mutation” (opens the source at this quote in a new tab)

Treatment

Dichloroacetate dose

“25 mg/kg/day” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using global assessment of treatment efficacy as the primary endpoint

Primary composite endpoint

“Global Assessment of Treatment Efficacy (GATE)” (opens the source at this quote in a new tab)

Endpoint validation

No evidence found.

Statistical analysis description

Number of participants (Planned and analyzed)

Enrollment

“30 patients” (opens the source at this quote in a new tab)

Description of analysis sets

No evidence found.

Results

Participant disposition

Early termination

“terminated early” (opens the source at this quote in a new tab)

Withdrawal of study medication by treatment arm

“During the initial 24-month treatment period, 15 of 15 patients randomized to DCA were taken off study medication, compared to 4 of 15 patients randomized to placebo.” (opens the source at this quote in a new tab)
“The clinical trial was terminated early because of peripheral nerve toxicity.” (opens the source at this quote in a new tab)

Baseline characteristics

No evidence found.

Efficacy results

Between-group difference in mean composite score

“not significantly different” (opens the source at this quote in a new tab)

Primary outcome and investigator conclusion on benefit

“The mean GATE score was not significantly different between treatment arms.” (opens the source at this quote in a new tab)
“Under these experimental conditions, the authors were unable to detect any beneficial effect.” (opens the source at this quote in a new tab)
“The findings show that DCA-associated neuropathy overshadows the assessment of any potential benefit in MELAS.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Discontinuations associated with neuropathy

“Study medication was discontinued in 17 of 19 patients because of onset or worsening of peripheral neuropathy.” (opens the source at this quote in a new tab)

Dose-level conclusion on peripheral nerve toxicity

“DCA at 25 mg/kg/day is associated with peripheral nerve toxicity resulting in a high rate of medication discontinuation and early study termination.” (opens the source at this quote in a new tab)

Study limitations

Summary

The trial enrolled 30 participants with MELAS and the A3243G mutation, not a PDCD population. It was terminated early, and the report documents peripheral neuropathy associated with 17 of 19 medication discontinuations. Its findings provide indirect safety information for chronic dichloroacetate exposure, but do not establish efficacy in PDCD.