Sodium Phenylbutyrate for Medium-Chain Acyl-CoA Dehydrogenase Deficiency

Overseen By Elizabeth McCracken

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Jerry Vockley, MD, PhD

Must not be taking: Corticosteroids, Valproic acid, Antimetabolites, others

Disqualifiers: Renal insufficiency, Diabetes, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called sodium phenylbutyrate to determine its effectiveness for individuals with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). MCADD is a genetic disorder that impairs the body's ability to break down certain fats into energy, particularly during fasting. The trial evaluates the safety and effectiveness of this medication, already approved for a similar disorder. Individuals with MCADD who have the specific genetic mutation c.985 A>G and can manage regular glucose monitoring may be suitable candidates for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in MCADD treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as those affecting kidney function, increasing protein breakdown, or raising ammonia levels, within 48 hours before starting and throughout the study. You also need to stop using sodium benzoate one week before starting. If you are on medications that can cause low potassium or affect glucose readings, you may not be eligible to participate.

Is there any evidence suggesting that sodium phenylbutyrate is likely to be safe for humans?

Research has shown that sodium phenylbutyrate, the treatment being tested, already has FDA approval for treating Urea Cycle Disorders. This approval confirms its safety for individuals with those conditions. Previous patients have demonstrated that sodium phenylbutyrate is generally well-tolerated, with most side effects being mild, such as an upset stomach or changes in taste. While specific information on its use for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is not yet available, its approval for another condition offers some reassurance about its safety. ^{1 2 3 4 5}

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

Researchers are excited about sodium phenylbutyrate for treating Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) because it offers a unique approach compared to current options like diet management and emergency glucose administration. Unlike these existing treatments, sodium phenylbutyrate targets the underlying metabolic process by potentially enhancing the removal of toxic fatty acid metabolites. This could lead to more effective management of symptoms and reduce the frequency of metabolic crises. By addressing the root cause rather than just managing symptoms, sodium phenylbutyrate has the potential to significantly improve the quality of life for those with MCADD.

What evidence suggests that sodium phenylbutyrate might be an effective treatment for MCADD?

Research has shown that sodium phenylbutyrate, a drug approved for treating urea cycle disorders, might also aid those with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). This medication helps the body eliminate ammonia, which can be harmful if it accumulates excessively. Earlier studies demonstrated health improvements in people with MCADD, suggesting its potential effectiveness for this condition. Although primarily used for another disorder, its mechanism may also benefit individuals with MCADD by addressing related metabolic issues. Participants in this trial will receive sodium phenylbutyrate to evaluate its effectiveness for MCADD. ^{1 4 6 7 8}

Who Is on the Research Team?

Gerard Vockley, MD, PhD

Principal Investigator

UPMC Children's Hospital of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for pediatric and adult patients aged 4 years or older with Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) due to a specific genetic mutation. Participants must have the common ACADM c.985 A>G (K304E) mutation.

Inclusion Criteria

Able to perform and comply with study activities including placement of a continuous glucose monitor, IV catheter, and all blood draws

Signed informed consent by the subject or parent/guardian of minors

I am not pregnant.

Exclusion Criteria

I have diabetes or take medication that can lower my blood sugar.

My kidney function is reduced.

I do not have any active infections or other ongoing health issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Run-in

Participants undergo training on the use of a continuous glucose monitor (CGM) and wear it for 10 days

10 days

Home-based

Treatment

Participants receive sodium phenylbutyrate (ACER-001) and undergo pharmacokinetics sampling

4 weeks

2 visits (in-person)

Follow-up

Study staff contact participants by phone to follow up on any adverse events

1 week

1 call (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Sodium Phenylbutyrate

Trial Overview The study tests Sodium Phenylbutyrate (ACER-001), already approved for Urea Cycle Disorders, on its safety and effectiveness in treating MCADD in individuals with the specified genetic mutation.

How Is the Trial Designed?

Group I: 4.0 g/m2/day BID sodium phenylbutyrate Experimental Treatment 1 Intervention

Up to 24 subjects (12: ages 4-9 years old; 12:10 years of age and older) will be randomized to take 4.0 g/m2/day divided into two daily doses

Who Is Running the Clinical Trial?

Jerry Vockley, MD, PhD

Lead Sponsor

Trials

6

Recruited

460+

Zevra Therapeutics

Industry Sponsor

Trials

4

Recruited

510+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06773026

NCT06773026 | Study of Sodium Phenylbutyrate (ACER ... This study will investigate the safety and efficacy (how well it works) of sodium phenylbutyrate in patients with MCADD. Detailed Description. Participation in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06069375?intr=AMMONAPS&aggFilters=studyType:int&viewType=Table&rank=5

Study of Sodium Phenylbutyrate (ACER-001) for the ... This study will investigate the safety and efficacy (how well it works) of sodium phenylbutyrate in patients with MCADD. Detailed Description. Participation in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3504130/

Evidence for involvement of medium chain acyl-CoA ... Sodium phenylbutyrate is used for treating urea cycle disorders, providing an alternative for ammonia excretion. Following conversion to its CoA ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1096719219306419

Clinical and biochemical outcomes of patients with medium ... Clinical and biochemical outcomes of patients with medium-chain acyl-CoA dehydrogenase deficiency ... Sodium phenylbutyrate improved the clinical state in ...

5. withpower.com withpower.com/trial/phase-2-lipid-metabolism-inborn-errors-10-2023-43d19

Sodium Phenylbutyrate for MCADD · Info for Participants Previous research suggests that sodium phenylbutyrate may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1424/

Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Individuals with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency typically appear normal at birth, and many are diagnosed through newborn screening ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/567129

Study of Sodium Phenylbutyrate (ACER-001) for the ... Previous research suggests that sodium phenylbutyrate may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how ...

8. withpower.com withpower.com/trial/sodium-phenylbutyrate-for-medium-chain-acyl-coa-dehydrogenase-deficiency-c847f

Sodium Phenylbutyrate for Medium-Chain Acyl-CoA ... ... Sodium Phenylbutyrate will have tolerable side effects & efficacy for patients with MCAD deficiency and Medium-Chain Acyl-CoA Dehydrogenase Deficiency. See