Folinic Acid for Language Impairment in Autism Spectrum Disorder

Not currently recruiting at 5 trial locations

Overseen By Richard Frye, MD, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Phoenix Children's Hospital

Must not be taking: Anticonvulsants, Bactrim, Valproic acid

Disqualifiers: Major depression, Bipolar, Psychotic disorder, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if folinic acid can improve language skills in children with autism spectrum disorder. While folinic acid reduces side effects during cancer treatment, its effectiveness for language issues in autism remains unknown. Participants will receive either folinic acid or a placebo (a substance with no active ingredients) to compare outcomes. Children with autism who face communication challenges and have a stable educational and speech therapy plan might be suitable for this study. As a Phase 2 trial, this research measures how well folinic acid works in an initial, smaller group of children with autism.

Will I have to stop taking my current medications?

The trial requires that your current medications remain stable, meaning no changes in the past 6 weeks and no planned changes for the next 6 months. However, if you are taking certain medications like Bactrim, valproic acid, or lamotrigine, you will need to stop them as they interfere with folate metabolism.

Is there any evidence suggesting that folinic acid is likely to be safe for humans?

Research has shown that folinic acid, also known as leucovorin, is generally safe for people. The FDA has approved it to help reduce side effects during cancer treatment. Studies have found that folinic acid can safely improve symptoms of autism spectrum disorder (ASD) in children, including better communication and behavior for some.

Specifically, research indicates that taking folinic acid orally is well-tolerated by children with ASD. While any treatment can have side effects, these studies have reported no major problems. This suggests folinic acid could be a promising option for addressing language issues in children with autism. ^{1 2 3 4 5}

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

Unlike the standard treatments for language impairment in autism, which often include behavioral therapies and medications like antipsychotics or stimulants, Folinic Acid offers a distinct approach. This treatment is derived from a form of vitamin B9, which targets metabolic pathways potentially involved in autism spectrum disorder. Researchers are excited because Folinic Acid may enhance language skills by improving brain function through its unique mechanism of supporting folate metabolism. Additionally, the treatment is administered orally in liquid form, which could be more accessible and easier to manage for children.

What evidence suggests that folinic acid might be an effective treatment for language impairment in autism?

Research has shown that folinic acid, which participants in this trial may receive, might improve language skills in children with autism who struggle with language. One study found that folinic acid helped these children communicate better. In another study, 85% of the children showed benefits, such as improved speech and communication. These findings suggest that folinic acid could aid language issues in autism. However, while early results are promising, more research is needed to confirm these benefits. Participants in this trial may also receive a placebo as part of the study design. ^{2 3 5 6 7}

Who Is on the Research Team?

Richard E Frye, MD, PhD

Principal Investigator

Rossignol Medical Center

Are You a Good Fit for This Trial?

This trial is for children aged 5 to less than 17.5 years with Autism Spectrum Disorder and language impairment, who speak English at home and have an IQ of at least 40 or a mental age of at least 18 months. They must be on stable speech therapy and educational plans, not planning medication changes for the study's duration, and not taking certain medications that affect folate metabolism.

Inclusion Criteria

You have a low score on a language test.

I weigh at least 15 kilograms.

My educational or treatment plan will not change for the next 3 months.

Exclusion Criteria

I have a mental health condition like depression or bipolar disorder.

I do not have any health conditions that would make it unsafe for me to take the study drug.

My child has stopped taking Bactrim for 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive folinic acid or placebo for 12 weeks under double-blind conditions

12 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Follow-up visits as per protocol

Open-label extension

Participants may opt into continuation of treatment with folinic acid for an additional 12 weeks

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Folinic Acid
• Placebo

Trial Overview The trial tests if folinic acid (leucovorin) can improve language problems in autistic children compared to a placebo. Folinic acid is FDA-approved for reducing chemotherapy side effects but its effectiveness in autism-related language issues is being investigated here over a period of up to 24 weeks.

How Is the Trial Designed?

Group I: Folinic Acid Experimental Treatment 1 Intervention

Subjects randomized to receive Folinic Acid will take Liquid levo-leucovorin via oral route. The target dose is 1 mg/kg/day with a maximum of 25 mg/day, divided in two daily doses. A two- to four-week supply of 15 ml vials will be dispensed in line with the visit schedule. With the exception of children in the lowest weight group (≥ 15 - \< 20 kg) from days 1-14, parents will administer the prescribed dose twice a day at the same time each day.

Group II: Placebo Control Placebo Group 1 Intervention

Subjects randomized to receive placebo will take placebo twice a day (Exception: children in the lowest weight group ( ≥ 15 - \< 20 kg) will start once a day for Days1-13). The pattern of dose escalation will be the same as the active compound. After 12 weeks, the blind will not be broken and subjects will be offered treatment for a 12-week open-label extension phase.

Folinic Acid is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Leucovorin for:

• Colorectal cancer
• Methotrexate overdose
• Megaloblastic anemia

Approved in United States as Leucovorin for:

• Colorectal cancer
• Methotrexate overdose
• Megaloblastic anemia

Approved in Canada as Calcium Folinate for:

• Colorectal cancer
• Methotrexate overdose
• Megaloblastic anemia

Approved in Japan as Calcium Folinate for:

• Colorectal cancer
• Methotrexate overdose
• Megaloblastic anemia

Who Is Running the Clinical Trial?

Phoenix Children's Hospital

Lead Sponsor

Trials

78

Recruited

5,014,000+

Southwest Autism Research & Resource Center

Lead Sponsor

Trials

9

Recruited

950+

Rossignol Medical Center

Lead Sponsor

Trials

6

Recruited

780+

Aprofol

Collaborator

Trials

1

Recruited

60+

State University of New York - Downstate Medical Center

Collaborator

Trials

67

Recruited

12,100+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Harvard University

Collaborator

Trials

237

Recruited

588,000+

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

Collaborator

Trials

2,103

Recruited

2,760,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39243316/

Efficacy of oral folinic acid supplementation in children with ... Oral folinic acid supplementation is effective and safe in improving ASD symptoms, with more pronounced benefits in children with high titers of folate ...

2. fda.gov fda.gov/news-events/press-announcements/fda-takes-action-make-treatment-available-autism-symptoms

FDA Takes Action to Make a Treatment Available for ... Individuals with cerebral folate deficiency have been observed to have developmental delays with autistic features (e.g., challenges with social ...

3. nature.com nature.com/articles/mp2016168

Folinic acid improves verbal communication in children ... Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02839915

NCT02839915 | Leucovorin for the Treatment of Language ... The purpose of this study is to determine the effectiveness of folinic acid in the treatment of language problems in children with autism spectrum disorder.

5. hhs.gov hhs.gov/press-room/autism-announcement-fact-sheet.html

Autism Announcement Fact Sheet Overall, 85% of patients experienced some type of clinical benefit including improved speech/communication capabilities. Efficacy data on the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40362912/

Safety and Efficacy of High-Dose Folinic Acid in Children ... High-dose folinic acid may be a promising intervention for children with ASD, and its efficacy is associated with folate metabolism gene polymorphisms.

7. aap.org aap.org/en/patient-care/autism/use-of-leucovorin-in-autistic-pediatric-patients/frequently-asked-questions-faqs-for-pediatricians-and-other-prescribing-pediatric-clinicians/?srsltid=AfmBOooKvnSeCIQigIzm1PqtTC8Q63aFn8cUam8OEfgBDVwONQdPJ12P

Leucovorin Use in Autism and Cerebral Folate Deficiency Small studies show benefits to communication and behavior for some autistic children, specifically those with CFD or evidence of folate ...