Folinic Acid for Language Impairment in Autism Spectrum Disorder

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

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing folinic acid, a vitamin, to see if it can help children with autism who have language problems. The study focuses on whether this vitamin can improve brain function and language skills. Children with moderate language issues will participate. Folinic acid has been studied for its potential to improve verbal communication in children with autism and language impairment.

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.

What evidence supports the effectiveness of the drug folinic acid for language impairment in children with autism spectrum disorder?

Research shows that folinic acid can improve verbal communication and social interaction in children with autism. In several studies, children taking folinic acid showed significant improvements in language and behavior compared to those taking a placebo, with no serious side effects reported. ^{1 2 3 4 5}

Is folinic acid safe for use in humans, particularly for those with autism spectrum disorder?

Folinic acid, also known as leucovorin, has been studied in children with autism spectrum disorder and is generally considered safe. Most studies report no serious adverse effects, with mild side effects like aggression, excitement, headache, insomnia, and increased tantrums occurring in some cases. ^{1 2 3 4 6}

How does the drug folinic acid differ from other treatments for language impairment in autism spectrum disorder?

Folinic acid is unique because it targets folate pathway abnormalities, which are common in children with autism spectrum disorder (ASD), especially those with folate receptor autoantibodies (FRAs). It can improve verbal communication and other ASD symptoms by bypassing the blockage in folate transport to the brain, offering a novel approach compared to other treatments that do not address this specific pathway. ^{1 2 3 4 7}

Research Team

Richard E Frye, MD, PhD

Principal Investigator

Rossignol Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. France pubmed.ncbi.nlm.nih.gov

Folinic acid improves the score of Autism in the EFFET placebo-controlled randomized trial. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Soluble Folate Receptor in Autism Spectrum Disorder: Relation to Autism Severity and Leucovorin Treatment. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Cerebral folate receptor autoantibodies in autism spectrum disorder. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. [2022]