Mitochondrial Cocktail for Autism Spectrum Disorder

(MitoASD Trial)

Overseen By Michael J Goldenthal, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Drexel University

Must not be taking: Anti-seizure medications

Disqualifiers: Ketogenic diet, Severe cognitive dysfunction, others

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

Compensation: Varies

Number of Visits: 9

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether treating mitochondrial dysfunction can affect symptoms of autism spectrum disorder (ASD) in children. The treatment, called the Mitochondrial Cocktail, consists of nutritional supplements and aims to improve cellular energy production. Researchers will assess the children's neurological and psychological health before, during, and after the treatment period to identify any improvements. Children aged 3 to 12 with a formal ASD diagnosis and suspected mitochondrial issues may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants on specialized diets or those needing anti-seizure medications. It's best to discuss your specific medications with the trial investigator.

Is there any evidence suggesting that the Mitochondrial Cocktail treatment is likely to be safe for children with ASD and mitochondrial dysfunction?

Research shows that the ingredients in the Mitochondrial Cocktail, such as ubiquinol, carnitine, and alpha-lipoic acid, are generally safe. Studies have found that taking 600 mg of alpha-lipoic acid daily was well-tolerated by 233 to 509 participants over periods ranging from six months to four years, with no major side effects reported.

Similarly, reviews indicate that alpha-lipoic acid and acetyl-L-carnitine (a type of carnitine) have been used safely in various clinical settings. This suggests that these ingredients, when combined in the Mitochondrial Cocktail, are likely safe to use. However, since this study is in an early phase, the main goal is to check safety, meaning researchers are still observing how well children handle the treatment.

Overall, past studies show that the individual ingredients are safe, but participants should report any side effects they notice during the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Mitochondrial Cocktail for autism spectrum disorder (ASD) because it targets mitochondrial dysfunction, which is a different approach from typical therapies that often focus on behavioral interventions or medications like antipsychotics. This experimental treatment combines ubiquinol, carnitine, and alpha-lipoic acid to bolster mitochondrial function, potentially addressing the underlying cellular energy issues that might contribute to ASD symptoms. By enhancing energy metabolism at the cellular level, the Mitochondrial Cocktail offers a novel strategy that could complement or enhance existing treatments.

What evidence suggests that the Mitochondrial Cocktail might be an effective treatment for ASD with mitochondrial dysfunction?

Research has shown that the Mitochondrial Cocktail, a mix of supplements like carnitine, Coenzyme Q10, and alpha-lipoic acid, may benefit children with autism spectrum disorder (ASD) who also have mitochondrial problems. One study found that this combination improved behavior scores in these children, although some benefits lessened over time. Another study reported that individuals with similar mitochondrial issues noticed improvements within 2 weeks to 3 months of starting these supplements. These nutrients aim to help cells produce energy, potentially stabilizing symptoms in neurological conditions. Overall, the cocktail is considered safe, with only mild side effects reported by some users. ^{5 6 7 8 9}

Who Is on the Research Team?

Michael J Goldenthal, PhD

Principal Investigator

Drexel University College of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

Subject/legal representative is considered reliable and capable of adhering to the protocol (e.g., able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the investigator.

Subject has a formal diagnosis of autistic spectrum disorders (ASD). the ASD diagnosis will satisfy the DSM- V criteria for ASD, and will be broad-spectrum including both severe and milder cases.

All subjects will have either suspected mitochondrial dysfunction as assessed by clinical evaluation, mitochondrial dysfunction as defined by the presence of significant abnormalities in their buccal mitochondrial respiratory complex activities (i.e., with either respiratory complex I or complex IV deficiencies) or have significantly aberrant specific activity ratios. Subjects with significant deficiencies in either muscle or skin fibroblast respiratory activities will also be included in those cases if buccal mitochondrial respiratory enzyme activity testing has not been performed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Mitochondrial Cocktail treatment at home once a day for 3 months

3 months

Evaluations at baseline and after 3 months

Non-treatment Observation

Participants are monitored without treatment for an additional 3 months

3 months

Evaluations at 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mitochondrial Cocktail

How Is the Trial Designed?

Group I: Mitochondrial Cocktail Experimental Treatment 1 Intervention

The precise content of the Mitochondrial Cocktail will be: * ubiquinol (liquid form, 150 mg/kg subject weight/day * carnitine, 50 mg/kg subject weight/day * alpha-lipoic acid, 100 mg/ day

Who Is Running the Clinical Trial?

Drexel University

Lead Sponsor

Trials

160

Recruited

48,600+

Published Research Related to This Trial

A study of 27,140 reported cases of rhabdomyolysis identified 14 drugs, including fenofibrate and risperidone, that are linked to mitochondrial toxicity, suggesting a common mechanism for drug-induced muscle damage.

Using murine L6 cells and human skeletal muscle-derived cells, researchers confirmed that these drugs cause significant mitochondrial dysfunction, indicating that the L6 model could be a useful and cost-effective tool for screening potential myotoxic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing In Vitro Models to Define the Role of Direct Mitochondrial Toxicity in Frequently Reported Drug-Induced Rhabdomyolysis. Bin Dayel, FF., Alfirevic, A., Chadwick, AE.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4264162/

Current Experience in Testing Mitochondrial Nutrients in ... Nine controlled clinical trials for CARN—mostly ALC—were conducted in a total of 384 patients with some neurological disorders, including Alzheimer's disease, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7774245/

Mitochondrial Medicine Therapies: Rationale, Evidence, and ... Mitochondrial medicine therapies aim to stabilize metabolic function, often using vitamins, antioxidants, and co-factors, to slow disease progression.

3. neurology.org neurology.org/doi/10.1212/WNL.90.15_supplement.P3.313

Effect of a Combination of Carnitine, Coenzyme Q10 and ... MitoCocktail reduced RCC I/IV ratio, improved some behavior scores, and may have therapeutic benefit in ASD, but some improvements waned after ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1096719216301275

Mitochondrial disease patients' perception of dietary ... The onset of perceived benefits was between 2 weeks to 3 months of initiating intake. Supplements seem to be safe, with only 28% of patients experiencing mild ...

5. researchgate.net researchgate.net/publication/376339460_Effect_of_a_Combination_of_Carnitine_Coenzyme_Q10_and_Alpha-Lipoic_Acid_MitoCocktail_on_Mitochondrial_Function_and_Neurobehavioral_Performance_in_Children_with_Autism_Spectrum_Disorder_P3313

Effect of a Combination of Carnitine, Coenzyme Q10 and ... Only one open-label trial treated 11 children with ASD and mitochondrial dysfunction with carnitine, coenzyme Q10 and alpha-lipoic acid.

6. ods.od.nih.gov ods.od.nih.gov/factsheets/PrimaryMitochondrialDisorders-HealthProfessional/

Dietary Supplements for Primary Mitochondrial Disorders Oral supplementation with 600 mg/day ALA for 6 months to 4 years was well tolerated in clinical trials of 233–509 people with diabetic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11302972/

A Comprehensive Review of Safety, Efficacy, and Indications ... Here we review two supplements, alpha-lipoic acid (ALA), also known as thioctic acid, and acetyl-L-carnitine (ALC), and data of treatment outcomes from the ...

8. umdf.org umdf.org/wp-content/uploads/2017/11/Supplements-and-Nutrition.pdf

Supplements and Nutrition - Mark A. Tarnopolsky Alpha-lipoic acid is an anti-oxidant located in the mitochondria with high theoretical potential for use in mitochondrial disease 1, although it has been ...

9. mitocanada.org mitocanada.org/wp-content/uploads/2021/06/Dietary-Supplements-for-Primary-Mitochondrial-Disorders-Health-Professional-Fact-Sheet.pdf

Dietary Supplements for Primary Mitochondrial Disorders Oral supplementation with 600 mg/day ALA for 6 months to 4 years was well tolerated in clinical trials of 233-509 people with diabetic.