What is the mechanism of action of this treatment?

Common treatments for Autism Spectrum Disorder (ASD) include pharmacological interventions like folinic acid, which is being studied for its potential to improve language problems in children with ASD. Folinic acid, also known as leucovorin, is believed to enhance neurotransmitter function and support metabolic processes that are often disrupted in ASD. Other treatments, such as melatonin, are used to address sleep disturbances by regulating the sleep-wake cycle. Understanding these mechanisms is crucial as it helps tailor treatments to target specific symptoms, potentially improving the quality of life for ASD patients by addressing core deficits and associated challenges.

What side effects are associated with this type of intervention?

Common treatments for Autism Spectrum Disorder (ASD) include behavioral and educational interventions, complementary and alternative therapies (CAM), and pharmacologic treatments. CAM therapies often lack high-quality evidence and can interact with prescription medications, leading to potential side effects. Specific CAM therapies like gluten-free casein-free diets may cause nutritional deficiencies. Pharmacologic treatments such as melatonin can improve sleep but may increase seizure risk in children with epilepsy. Antipsychotics and mood stabilizers used for behavioral issues can cause weight gain, metabolic changes, and sedation.

What prior FDA approvals exist?

Currently, there are no FDA-approved medications specifically for improving language problems in children with Autism Spectrum Disorder (ASD). However, some medications are approved to address associated symptoms such as irritability and aggression. For example, risperidone and aripiprazole are FDA-approved for treating irritability in children with ASD. Folinic acid, also known as leucovorin, is being studied for its potential to improve language problems in children with ASD, but it is not yet FDA-approved for this use.

What other types of research exist?

Promising novel alternatives to folinic acid for treating language problems in children with autism spectrum disorder include Palmitoylethanolamide, which has shown potential in improving cognitive functions, behaviors, and sociability, and Omega-3 supplementation, which has anecdotal evidence of benefits despite mixed results in clinical trials. Additionally, prolonged-release melatonin has demonstrated efficacy and safety in managing sleep disturbances, which can indirectly benefit overall behavior and cognitive function in children with ASD.

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Folinic Acid for Language Impairment in Autism Spectrum Disorder

Phase 2

Waitlist Available

Led By Richard Frye, MD, PhD

Research Sponsored by Phoenix Children's Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Weight ≥ 15 kg

Stable medication (no changes in past 6 weeks and no planned changes for the next 6 months (duration of the study)

Must not have

Significant medical condition by history or by physical examination or lab tests that would be incompatible with the study drug

Presence of serious behavioral problems (tantrums, aggression, self-injury) for which another treatment is warranted

Timeline

Screening 3 weeks

Treatment Varies

Follow Up pre-treatment, 12 weeks(optional), and 24weeks (or early termination)

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While the specific side effects are not listed here, as folinic acid is generally used during cancer treatment to reduce side effects from chemotherapy, it may be well-tolerated. However, potential risks will likely be monitored given its investigational use.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I weigh at least 15 kilograms.

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My medications have been the same for the last 6 weeks and won't change during the study.

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I have been in a stable speech therapy program for at least a month with no changes expected for the next 12 weeks.

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I am between 5 and 17 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have serious behavioral issues that need treatment.

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My child is on medication for seizures.

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My child takes more vitamins or minerals than the daily amount recommended.

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I am not taking valproic acid, its derivatives, or lamotrigine.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ pre-treatment, 12 weeks(optional), and 24weeks (or early termination)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~pre-treatment, 12 weeks(optional), and 24weeks (or early termination)

This trial's timeline: 3 weeks for screening, Varies for treatment, and pre-treatment, 12 weeks(optional), and 24weeks (or early termination) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Clinical Evaluation of Language Fundamentals 4 (CELF-4) Score.

Change in Clinical Evaluation of Language Fundamentals Preschool (CELF-P) score

Secondary study objectives

Change in Clinician Global Impression for Improvement (CGI-I) Score

Other study objectives

Change in Aberrant Behavior Checklist (ABC) Score

Change in folate gene expression

Change in in methylation

+3 more

Side effects data

From 2016 Phase 3 trial • 1072 Patients • NCT01183780

60%

Diarrhoea

50%

Nausea

48%

Fatigue

38%

Decreased appetite

35%

Neutropenia

34%

Epistaxis

31%

Stomatitis

30%

Constipation

29%

Alopecia

29%

Vomiting

28%

Hypertension

26%

Neutrophil count decreased

23%

Abdominal pain

22%

Oedema peripheral

18%

Anaemia

18%

Proteinuria

17%

Mucosal inflammation

16%

Pyrexia

15%

Thrombocytopenia

15%

Headache

15%

Platelet count decreased

14%

Asthenia

14%

Weight decreased

13%

Palmar-plantar erythrodysaesthesia syndrome

13%

Cough

11%

Dyspnoea

White blood cell count decreased

Insomnia

Rash

Back pain

Malaise

Dysgeusia

Blood alkaline phosphatase increased

Hypoalbuminaemia

Hypokalaemia

Upper respiratory tract infection

Pain in extremity

Dizziness

Hiccups

Arthralgia

Aspartate aminotransferase increased

Dehydration

Dysphonia

Urinary tract infection

Peripheral sensory neuropathy

Dry skin

Alanine aminotransferase increased

Dyspepsia

Haemorrhoids

Proctalgia

Abdominal distension

Febrile neutropenia

Intestinal obstruction

Pulmonary embolism

Sepsis

International normalised ratio increased

Nephrotic syndrome

Fall

Renal failure acute

Haematemesis

Ileus

Small intestinal obstruction

Blood bilirubin increased

Pneumonia

Large intestinal obstruction

Large intestine perforation

Venous thrombosis

Clostridium difficile colitis

Gastritis

Intestinal perforation

General physical health deterioration

100%

80%

60%

40%

20%

Study treatment Arm

FOLFIRI + Ramucirumab

FOLFIRI + Placebo

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Folinic AcidExperimental Treatment1 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 ControlPlacebo Group1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Folinic Acid

2015

Completed Phase 3

~4380

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Autism Spectrum Disorder (ASD) include pharmacological interventions like folinic acid, which is being studied for its potential to improve language problems in children with ASD. Folinic acid, also known as leucovorin, is believed to enhance neurotransmitter function and support metabolic processes that are often disrupted in ASD. Other treatments, such as melatonin, are used to address sleep disturbances by regulating the sleep-wake cycle. Understanding these mechanisms is crucial as it helps tailor treatments to target specific symptoms, potentially improving the quality of life for ASD patients by addressing core deficits and associated challenges.

Folic acid as an adjunct in the treatment of children with the autism fragile-X syndrome (AFRAX).Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis.Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial.