Leucovorin for Autism

Recruiting at 2 trial locations

Overseen By Sophia Crisler

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Phoenix Children's Hospital

Must not be taking: Chemotherapy, Antimalarial, Immunosuppressive, Antibiotics

Disqualifiers: Epilepsy, Genetic syndromes, Liver disease, others

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

Compensation: Varies

Number of Visits: 3

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether a liquid form of leucovorin calcium (a form of folinic acid) can improve social communication and other core symptoms in young children with autism spectrum disorder (ASD). Researchers will compare leucovorin's effects with a placebo to assess any noticeable differences in behavior and cognitive skills. The trial suits children aged 2.5 to 5 years with confirmed ASD, social communication delays, and language impairments. Participants must maintain their current dietary and behavioral treatments throughout the study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of children, contributing to early findings on its potential benefits.

Will I have to stop taking my current medications?

The trial requires that you keep your current treatments, including medications, the same for the study period and that they have not changed for two months before starting the study. However, you cannot take certain drugs that interact with leucovorin, like some chemotherapy agents, antimalarial drugs, immune suppressants, and specific antibiotics.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that leucovorin calcium, a treatment used in the trial, is generally well-tolerated. Studies have found that doses between 0.5 to 2 mg/kg/day can improve symptoms like behavior and thinking in people with autism. Importantly, these studies did not identify any major safety concerns with leucovorin calcium, suggesting it is safe at these doses.

Additionally, the FDA has already approved leucovorin calcium for other conditions, providing extra confidence in its safety. This approval indicates thorough testing for safety in humans for those conditions. However, more research is needed to fully understand its effects specifically 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 autism, which often focus on behavioral therapies and medications aimed at managing symptoms, levoleucovorin calcium offers a unique approach by targeting underlying metabolic pathways. This treatment is a form of folate, which is crucial for brain development and neurotransmitter function, potentially addressing core symptoms of autism rather than just the secondary ones. Researchers are excited about levoleucovorin because it may improve communication and social interactions by enhancing brain function at the cellular level, offering a promising alternative or complement to existing therapies.

What evidence suggests that leucovorin calcium might be an effective treatment for autism?

Research has shown that leucovorin calcium, also known as folinic acid, might improve symptoms in children with autism spectrum disorder (ASD). Some studies have found that it can enhance language and behavior in children with ASD. This trial will compare leucovorin calcium with a placebo. Leucovorin addresses issues in the body's use of folate, which are linked to autism symptoms. Early findings suggest that leucovorin may improve social communication and reduce core symptoms of ASD. While more research is needed, these early results are promising for those considering this treatment. ^{1 2 4 5 6}

Who Is on the Research Team?

Richard E Frye, MD, PhD

Principal Investigator

Rossignol Medical Center, Phoenix AZ

Are You a Good Fit for This Trial?

This trial is for young children aged 2.5 to 5 years with confirmed autism spectrum disorder (ASD) who have social and communication delays, can attend to social stimuli, tolerate imaging procedures, and are being raised with English included in their languages. They must not change any ongoing treatments during the study and should have a moderate or higher level of autism severity.

Inclusion Criteria

Folate Receptor Alpha Autoantibody Positive status

Ability to attend to social stimulus and tolerate imaging procedures, as determined at the discretion of the investigator

English included in the languages in which the child is being raised

Exclusion Criteria

You have a specific genetic condition or syndrome.

You have a history of hurting yourself or others, or show signs of thinking about or planning to harm yourself.

You have epilepsy, a condition that causes seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive either placebo or active treatment for 12 weeks under double-blind conditions

12 weeks

Regular visits for monitoring and assessments

Treatment Phase 2

All participants receive active treatment for an additional 12 weeks

12 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Levoleucovorin Calcium
• Placebo

Trial Overview The trial is testing liquid leucovorin calcium against a placebo to see if it improves social communication and other symptoms of ASD in children. The study will enroll 80 participants across two sites for about half a year, from screening to end of treatment.

How Is the Trial Designed?

Group I: L-leucovorin calcium Experimental Treatment 1 Intervention

The liquid form of leucovorin calcium will be dosed by weight, with a target dose of 1mg/kg/day, divided into two daily doses. This product may be taken alone or mixed with liquid. Participants randomized to this arm will receive active treatment for both 12-week phases of the study.

Group II: Placebo Placebo Group 1 Intervention

The placebo will mimic the experimental treatment in flavor, odor, packaging, and dosing instructions. Participants randomized to this arm will receive placebo for the first 12 weeks of the study, then active treatment for the remaining 12 weeks.

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+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

New York State Institute for Basic Research

Collaborator

Trials

7

Recruited

960+

State University of New York - Downstate Medical Center

Collaborator

Trials

67

Recruited

12,100+

Autism Speaks

Collaborator

Trials

36

Recruited

3,800+

Published Research Related to This Trial

A systematic review of 13 studies found that reducing the dose of leucovorin in chemotherapy regimens combining it with fluorouracil does not significantly impact the efficacy of treatment for colorectal cancer.

Lower doses of leucovorin also do not increase the frequency or severity of adverse effects, and in some cases, higher doses were associated with more side effects, indicating that dose adjustments may be a safe alternative during drug shortages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High vs. low-dose leucovorin in regimens with fluorouracil in colorectal cancer therapy. Juřica, J., Šuverová, P., Goněc, R., et al.[2023]

Citations

1. 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 ... The U.S. Food and Drug Administration today initiated the approval of leucovorin calcium tablets for patients with cerebral folate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7477301/

Treatment of Folate Metabolism Abnormalities in Autism ... This article reviews one of these treatments, d,l-leucovorin calcium (also known as folinic acid) for treatment of folate pathway abnormalities in children ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04060030

Study Details | NCT04060030 | Treatment of Social and ... The primary objective of this study is to evaluate the cognitive and behavioral effects of liquid leucovorin calcium on young children with autism spectrum ...

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

Efficacy of oral folinic acid supplementation in children with ... Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials ...

5. fagronacademy.us fagronacademy.us/blog/leucovorin-and-autism-spectrum-disorder

Leucovorin and Autism Spectrum Disorder Explore how leucovorin calcium (folinic acid) may improve language and behavioral symptoms in children with autism spectrum disorder.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04060017

NCT04060017 | Early Treatment of Language Impairment ... The primary aim of this study is to evaluate the effect of a liquid form of leucovorin calcium on language impairments in very young children with ASD.