Arbaclofen vs. Placebo in the Treatment of Children and Adolescents With ASD (ARBA)

(ARBA Trial)

Recruiting at 3 trial locations

Overseen By Lisa Genore

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Evdokia Anagnostou

Must not be taking: Baclofen, Vigabatrin, Tiagapine, others

Disqualifiers: Pregnancy, Serious medical conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will test if arbaclofen can improve social skills in children and teenagers with Autism Spectrum Disorder (ASD). Currently, there are no medications specifically for social difficulties in ASD. Arbaclofen might help by balancing brain chemicals involved in social behavior. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech.

Will I have to stop taking my current medications?

If you are already on stable medications affecting behavior, you can continue them as long as they haven't changed in the last 6 weeks and won't change during the study. However, you cannot take certain medications like racemic baclofen, vigabatrin, tiagapine, riluzole, clobazam, or regular benzodiazepines.

What safety data exists for Arbaclofen and similar treatments?

Adverse events (unwanted effects) in clinical trials are often compared to placebo (a dummy treatment with no active drug) to understand safety. In healthy volunteers, common side effects during placebo treatment included headache, drowsiness, and weakness, with an overall incidence of 19%. This suggests that some side effects may occur even without active medication. ^{1 2 3 4 5}

How does the drug Arbaclofen differ from other treatments for this condition?

Arbaclofen, like baclofen, is a GABA B receptor agonist, which means it works by activating specific receptors in the brain to reduce pain or other symptoms. This mechanism is different from many other treatments that might not target these receptors. While baclofen has shown mixed results in pain management in humans, its unique action on GABA B receptors could offer a novel approach for conditions where other treatments are ineffective. ^{6 7 8 9 10}

Research Team

Evdokia Anagnostou, M.D

Principal Investigator

Holland Bloorview Kids Rehabilitation Hospital

Robert Nicolson, M.D

Principal Investigator

University of Western Ontario, Lawson Health Research Institute

Julia Frei, M.D

Principal Investigator

McMaster University, Offord Centre for Child Studies

Muhammad Ayub, M.D

Principal Investigator

Queen's University

Eligibility Criteria

Inclusion Criteria

Outpatients 5-17 years of age inclusive.

Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). DSM-5 criteria will be established by a clinician with expertise with individuals with ASD. Diagnosis will be supported by the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).

Complex language to qualify for ADOS-2 modules 3 or 4.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive arbaclofen or placebo to assess its effect on social function in children and adolescents with ASD

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Arbaclofen
• Placebo

Participant Groups

Group I: Arbaclofen Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Evdokia Anagnostou

Lead Sponsor

Trials

12

Recruited

640+

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Queen's University

Collaborator

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Holland Bloorview Kids Rehabilitation Hospital

Collaborator

Trials

69

Recruited

14,100+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

University of Western Ontario, Canada

Collaborator

Trials

168

Recruited

320,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Findings from Research

The study analyzed adverse event (AE) data from six randomized controlled trials involving schizophrenia treatments, highlighting that the absolute prevalence and expected duration of AEs provide a more comprehensive understanding of a drug's safety compared to just incidence rates.

Using a new metric to assess the drug-placebo difference in AE prevalence, the research found that some AEs not listed in the standard drug label significantly impacted drug tolerability, suggesting that including these metrics in drug labels could enhance safety signal detection and inform better treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Method for Deriving Adverse Event Prevalence in Randomized Controlled Trials: Potential for Improved Understanding of Benefit-Risk Ratio and Application to Drug Labels. Piacentino, D., Ogirala, A., Lew, R., et al.[2023]

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

References

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

A Novel Method for Deriving Adverse Event Prevalence in Randomized Controlled Trials: Potential for Improved Understanding of Benefit-Risk Ratio and Application to Drug Labels. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. [2019]

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

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. [2023]

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

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The SIDER database of drugs and side effects. [2022]

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

Is baclofen an analgesic? [2019]

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

Oral baclofen reduces visceral pain-related pseudo-affective responses to colorectal distension in rats: relation between plasma exposure and efficacy. [2013]

8. India pubmed.ncbi.nlm.nih.gov

GABA B mediated analgesia in tonic pain in monkeys. [2013]

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

Baclofen for alcohol use disorder-a systematic meta-analysis. [2019]

10. Spain pubmed.ncbi.nlm.nih.gov

Baclofen analgesia in mice: a GABAB-mediated response. [2016]