Leucovorin for the Treatment of Language Impairment in Children With Autism Spectrum Disorder
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02839915|
Recruitment Status : Not yet recruiting
First Posted : July 21, 2016
Last Update Posted : August 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|Autism Spectrum Disorder||Drug: Folinic Acid Other: Placebo||Phase 2|
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder often with life-long consequences that affects young children during critical developmental periods. The Centers for Disease Control estimates that ASD affects as many as 14.7 per 1000 children (1 in 68). Despite the dramatic rise in the detected prevalence of ASD over the past two decades, no effective medical treatment has been developed to address core ASD symptoms (social communication and repetitive behavior), the closely associated problem of language impairment, or the underlying pathophysiology of ASD. Currently, the only accepted treatment for core ASD symptoms is behavior therapy, which may entail intensive one-on-one treatment over several years.
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. Folinic acid, also known as leucovorin, is approved by the U.S. Food and Drug Administration (FDA) to decrease side effects during cancer chemotherapy. Folinic acid may be helpful in treating language problems in children with autism spectrum disorder, but this is not known. Therefore, folinic acid is an investigational new drug for this study.
The primary aims of this study are to evaluate the efficacy and tolerability of high-dose folinic acid for improving the closely associated symptoms of language impairment in children with autism spectrum disorder (ASD). Improvement in delayed language may also benefit the core ASD problem of social communication. The study will also focus on identification of biomarkers in pre-specified subgroups of children with ASD that may moderate positive response to folinic acid. The study model is that high-dose folinic acid will improve language and set the stage for improved social communication in children with ASD and moderate language impairment. To test whether folinic acid is superior to placebo, 162 children (age 5 to 12 yrs 6 months, inclusive) with ASD and moderate language will be randomly assigned to folinic acid or placebo for 12 weeks under double-blind conditions. The study team will also test whether abnormalities in folate-dependent pathways, such as dysfunctional transport of folate across the blood-brain barrier, will moderate positive response to folinic acid treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||162 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Leucovorin for the Treatment of Language Impairment in Children With Autism Spectrum Disorder|
|Estimated Study Start Date :||October 2019|
|Estimated Primary Completion Date :||January 1, 2022|
|Estimated Study Completion Date :||January 1, 2023|
Experimental: Folinic Acid
Subjects randomized to receive Folinic Acid will take one capsule, twice a day. Once in the morning and once in the evening (Exception: children in the lowest weight group ( ≥ 15 - < 20 kg) will start with 10 mg capsule once a day for Days1-13). Dosing will start at 10-20 mg/day, based on subject's weight, and increase to 30-50 mg/day over four weeks. Primary caregiver will be contacted by telephone on Weeks 2, 6 and 10. Follow up visits at Weeks 4, 8 and 12 (end of Double-blind phase). After 12 weeks, the blind will not be broken and subjects will be offered treatment for a 12-week open-label extension phase.
Drug: Folinic Acid
Capsule form, taken twice a day with a max dose of 50 mg
Other Name: Leucovorin
Placebo Comparator: Placebo Control
Subjects randomized to receive placebo will take one capsule, twice a day (Exception: children in the lowest weight group ( ≥ 15 - < 20 kg) will start with capsule once a day for Days1-13). The pattern of dose escalation will be the same as the active compound. Primary caregiver will be contacted by telephone on Weeks 2, 6 and 10. Follow up visits at Weeks 4, 8 and 12 (end of Double-blind phase). After 12 weeks, the blind will not be broken and subjects will be offered treatment for a 12-week open-label extension phase.
Inactive placebo comparator
- Change in Core-Clinical Evaluation of Language Fundamentals (Core-CELF) Score [ Time Frame: Screening, Week 12 ]The Core-CELF is comprised of 4 subtests intended to identify language problems and can be used to track progress over time. Administration of the CELF takes 30-45 minutes. The Core-CELF score is a composite that includes receptive and expressive language. Using the tables in the manual, raw scores from the four subtests are compared to normative data by age. The population mean = 100 + 15.
- Change in Clinician Global Impression for Improvement (CGI-I) Score [ Time Frame: Up to 12 Weeks ]The CGI-I is a 7-point measure of overall symptomatic change compared to baseline that will be used as a key secondary outcome measure. Scores range from 1 (Very Much Improved) through 4 (Unchanged) to 7 (Very Much Worse). The CGI-I will be rated by a clinician who is blind to treatment assignment, and will not engage in discussion of adverse events and medication dose. Ratings of "Much Improved" or "Very Much Improved" on the CGI-I will be used to define positive response. Subjects who drop out will be rated as non-responders.
- Change in Aberrant Behavior Checklist (ABC) Score [ Time Frame: Up to 12 Weeks ]The ABC is a 58-item consisting five subscales: hyperactivity, irritability, social withdrawal, stereotypic behavior and inappropriate speech in children with developmental disabilities. A higher score indicates more frequent aberrant behaviors.
- Home Situations Questionnaire- Modified for ASD (HSQ-ASD): [ Time Frame: Up to 12 Weeks ]The HSQ-ASD is a parent-rated scale of child noncompliance. The parent reports on the child's difficulties with compliance in 24 everyday situations. Questions answered affirmatively are then rated on a 1 to 9 Likert scale, with higher scores indicating more severe noncompliance. The scale yields a count of "yes" responses (0 to 27) and a severity score (total of 1 through 9 for all "yes" responses, for a range of 0 to 216
- Children's Yale-Brown Obsessive-Compulsive Scales-ASD (CYBOCS-ASD) [ Time Frame: Up to 12 Weeks ]The CYBOCS-ASD is a modified version of the CYBOCS developed for use in children with Obsessive-Compulsive Disorder. Each item is scored from 0 (least symptomatic) to 4 (most symptomatic), yielding a Total score from 0 to 20. It has established reliability and validity65 and is sensitive to change.66
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02839915
|Contact: Nichole Evans, MS||404-785-9345||Andrea.Evans@choa.org|
|Contact: Lawrence Scahill, MSN, PhDemail@example.com|
|United States, Arizona|
|Phoenix Children's Hospital||Not yet recruiting|
|Phoenix, Arizona, United States, 85016|
|Contact: Richard Frye, MD, PhD 602-933-1000|
|Principal Investigator: Richard Frye, MD, PhD|
|United States, Georgia|
|Children's Healtcare of Atlanta||Not yet recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Nichole Evans, MS 404-785-9345 Andrea.Evans@choa.org|
|Contact: Lawrence Scahill, PhD 404-785-9400 Lawrence.firstname.lastname@example.org|
|Principal Investigator: Lawrence Scahill, PhD|
|United States, Massachusetts|
|Harvard University||Not yet recruiting|
|Lexington, Massachusetts, United States, 02421|
|Contact: Jennifer Mullett, RN 781-860-1700 JMULLETT@mgh.harvard.edu|
|Contact: Christopher Christopher, MD 781-860-1700 CMCDOUGLE@mgh.harvard.edu|
|Principal Investigator: Christopher Christopher, MD|
|Principal Investigator:||Richard Frye, MD, PhD||Phoenix Children's Hospital|