Gabapentin for Autism

Overseen By Taylor Merk

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: David Cochran

Must not be taking: Opioids, Benzodiazepines

Disqualifiers: Neurological, Genetic, Psychotic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether gabapentin (Neurontin) can improve social skills in teens with autism by balancing certain brain chemicals. Researchers aim to determine if increasing GABA, a calming brain chemical, enhances social interactions. Participants will take gabapentin for 8 weeks, with brain scans conducted before and after to measure changes. Teens aged 13-17 with autism, a basic understanding of English, and no other neurological disorders might be suitable for this study. As a Phase 4 trial, gabapentin is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are on medications that cause respiratory depression, like opioids or benzodiazepines, or if you are currently being treated with gabapentin.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking medications that cause respiratory depression or if you are already on gabapentin.

What is the safety track record for gabapentin?

Research has shown that gabapentin has been studied for its safety in people with seizures and other conditions. Common side effects include sleepiness, dizziness, or fatigue. However, some reports indicate that gabapentin causes no side effects when treating challenging behaviors in autism, suggesting it is generally well-tolerated for this purpose. Additionally, gabapentin's approval for other conditions provides some reassurance about its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for autism, which often include behavioral therapy and medications like antipsychotics or stimulants, gabapentin offers a different approach. Gabapentin, originally used for nerve pain and seizures, works by calming overactive neurons in the brain. Researchers are excited about gabapentin because it may help reduce irritability and anxiety in individuals with autism, potentially improving social interaction and communication. This unique mechanism could complement existing therapies, offering a novel option for managing symptoms.

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

Research has shown that gabapentin effectively treats certain conditions and might assist with social challenges in autism spectrum disorder (ASD). Studies have found that gabapentin can increase levels of GABA, a calming brain chemical, in areas of the brain related to social skills. This is significant because people with ASD often experience an imbalance in these brain chemicals. Early findings suggest this treatment might improve social behaviors in teenagers with ASD by addressing this imbalance. Gabapentin's potential to reduce self-harming behaviors in those with ASD also indicates it could help manage other symptoms. Overall, promising evidence suggests gabapentin could enhance social skills in people with ASD. Participants in this trial will receive an 8-week open-label treatment with gabapentin to further evaluate its effects. ^{2 3 6 7 8}

Who Is on the Research Team?

David Cochran, MD

Principal Investigator

UMass Medical School

Are You a Good Fit for This Trial?

This trial is for English-speaking adolescents aged 13-17 with Autism Spectrum Disorder and an IQ over 70. They must be able to give informed assent, with a guardian's consent, and not have genetic disorders like Fragile X or Rett Syndrome. Participants should not have metal implants, severe claustrophobia, unstable psychiatric conditions requiring medication changes during the study, significant medical illnesses, renal dysfunction or be pregnant.

Inclusion Criteria

For sexually active females, agreement to use two forms of contraception during trial to avoid pregnancy

Meets DSM-5 criteria for Autism Spectrum Disorder

IQ >70 per Weschler Abbreviated Scale of Intelligence (WASI)

Exclusion Criteria

History of psychotic disorder

History of intolerance to gabapentin or pregabalin

I am taking medications that can slow my breathing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Acute Response Assessment

Single dose challenge of gabapentin to evaluate immediate GABA response

1 day

1 visit (in-person)

Treatment

8-week open-label treatment with gabapentin to assess sustained GABA response and clinical improvements

8 weeks

Visits at baseline, Weeks 2, 4, and 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gabapentin

Trial Overview

The trial tests Gabapentin in adolescents with ASD to see if it can increase GABA levels in the brain and improve social cognition. It involves an initial single dose challenge followed by an 8-week treatment period where effects on GABA levels and social cognition are measured using magnetic resonance spectroscopy (MRS).

How Is the Trial Designed?

Group I: Gabapentin Open-label treatment Experimental Treatment 1 Intervention

8-week treatment with gabapentin

Gabapentin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Neurontin for:

• Postherpetic neuralgia
• Partial-onset seizures

Approved in European Union as Gabapentin for:

• Peripheral neuropathic pain
• Partial-onset seizures

Approved in Canada as Gabapentin for:

• Postherpetic neuralgia
• Partial-onset seizures

Who Is Running the Clinical Trial?

David Cochran

Lead Sponsor

Trials

1

Recruited

40+

Eagles Autism Foundation

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

Gabapentin is a new antiepileptic drug approved for use as an add-on treatment for patients with partial or secondarily generalized seizures that are not well controlled by standard antiepileptic medications.

Similar to lamotrigine, gabapentin offers an additional option for patients struggling to manage their seizures effectively with existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin--a new antiepileptic drug. [2018]

Gabapentin (GBP) was found to be effective as an add-on therapy for refractory partial seizures in children aged 3-12 years, showing a significant reduction in seizure activity compared to placebo, particularly for complex partial and secondarily generalized seizures.

The treatment was well tolerated, with a notable percentage of patients reporting improvements in seizure frequency according to both investigator and parent assessments, indicating its potential as a safe option for managing difficult-to-treat seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Gabapentin Paediatric Study Group. Appleton, R., Fichtner, K., LaMoreaux, L., et al.[2019]

In a 20-week study involving 141 patients with partial seizures, gabapentin significantly reduced seizure frequency, with 71% of participants experiencing a 50% or greater decrease in seizures, and 46% becoming seizure-free in the last 8 weeks.

Gabapentin also improved quality of life, as shown by significant enhancements in 5 out of 10 questions on the QOLIE-10 questionnaire, indicating that it not only helps with seizure control but also positively affects patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome evaluation of gabapentin as add-on therapy for partial seizures. "NEON" Study Investigators Group. Neurontin Evaluation of Outcomes in Neurological Practice. Bruni, J.[2018]

Gabapentin, commonly used for various conditions, may cause hypoglycemia even in patients without diabetes, as demonstrated by a case report of a 47-year-old woman who experienced severe low blood sugar after starting the medication.

The potential mechanism for this hypoglycemia could involve gabapentin's interaction with voltage-gated calcium channels in the pancreas, suggesting a need for further research into this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Case Report: Gabapentin-Induced Hypoglycemia. Hayes, WJ., Ferdinand, A., Neabore, S., et al.[2022]

A review of studies on pharmacological treatments for autism in adolescents and adults found that while some medications, like haloperidol and risperidone, show effectiveness in managing symptoms, there is a lack of controlled studies validating their safety and efficacy.

The review highlights that autism may involve dysfunctions in neuromediation systems, particularly with serotonin and dopamine, suggesting that future research should focus on these systems to develop more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Review of psychopharmacological treatments in adolescents and adults with autistic disorders]. Baghdadli, A., Gonnier, V., Aussilloux, C.[2007]

Gabapentin, commonly prescribed for neuropathic pain, lacks sufficient evidence for its safety and efficacy, as many trial results, particularly regarding its harms, have not been fully reported.

This study aims to analyze and disclose adverse events from six previously unreported trials of gabapentin, using clinical study reports and individual participant data to provide a clearer understanding of its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoring invisible and abandoned trials of gabapentin for neuropathic pain: a clinical and methodological investigation. Mayo-Wilson, E., Chen, X., Qureshi, R., et al.[2022]

While there are no medications specifically approved for treating autism, some medications like haloperidol and risperidone can help manage associated symptoms, although they may cause significant side effects.

Current treatments focus on alleviating specific symptoms, such as hyperactivity, rather than addressing the core social and communication challenges of autism, as no medications have been proven effective for those core symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapeutic management of autism. Posey, DJ., McDougle, CJ.[2022]

In a 12-week randomized, placebo-controlled trial involving 121 children with autism, memantine did not show significant clinical efficacy in improving symptoms, although it was well-tolerated with only mild to moderate adverse effects reported.

The study found that while memantine was safe and tolerable, it did not lead to improvements in the primary outcome measure of social responsiveness, and one communication measure even worsened in the memantine group compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension. Aman, MG., Findling, RL., Hardan, AY., et al.[2022]

Naltrexone has been found to be effective in reducing self-injurious behavior and may also help with hyperactivity, irritability, and social withdrawal in pediatric patients with autistic disorder, based on a review of 25 studies including case reports and clinical trials.

The most common side effect reported was transient sedation, and no serious adverse effects were noted in short-term studies, suggesting that naltrexone may be a safe option for children with autism, especially when other treatments have not worked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of naltrexone use in pediatric patients with autistic disorder. Elchaar, GM., Maisch, NM., Augusto, LM., et al.[2013]

A 44-year-old woman developed new-onset non-ischaemic cardiomyopathy after two months of gabapentin therapy, with a significantly reduced ejection fraction of 36%.

This case raises concerns about a potential link between gabapentin and cardiomyopathy, although current literature does not establish a known risk of gabapentin causing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A rare case of a gabapentin-induced cardiomyopathy. Tellor, KB., Ngo-Lam, R., Badran, D., et al.[2019]

Gabapentin is an effective add-on therapy for patients over 12 years old with refractory partial seizures, showing positive results in three multicenter, placebo-controlled trials involving 705 patients.

The drug has a favorable safety profile, with no significant toxic effects on the hematopoietic system, liver, or kidneys, and it does not interact with other medications due to its lack of protein binding and metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gabapentin (Neurontin): a new possibility in the add-on therapy of partial epilepsies]. Krämer, G.[2018]

Gabapentin is effective as an adjunct treatment for complex partial seizures in both adults and children, but it shows the most benefit in adults when used at higher doses as monotherapy.

The drug has a low incidence of adverse effects and a favorable pharmacokinetic profile, making it safer with fewer drug interactions compared to traditional anti-epileptic drugs, although it can cause negative behavioral effects in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin: a unique anti-epileptic agent. Dougherty, JA., Rhoney, DH.[2018]

Gabapentin (GBP) as an add-on therapy significantly reduced the frequency of refractory partial seizures in patients, with a 21.8% reduction in seizure frequency for the 900 mg/day group compared to only 0.3% in the placebo group, based on a study of 272 patients over 12 weeks.

While 69% of patients in the 900 mg/day group experienced adverse events, the most common being somnolence, dizziness, and fatigue, there were no significant safety concerns regarding liver or blood health, indicating that gabapentin is generally well-tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group. Anhut, H., Ashman, P., Feuerstein, TJ., et al.[2019]

Gabapentin's gastroretentive formulation (G-GR, Gralise®) allows for once-daily dosing of 1800 mg with better tolerability and a shorter titration period compared to the immediate-release formulation (G-IR), which requires three divided doses.

The differences in dosing and tolerability between G-GR and G-IR are attributed to their distinct pharmacokinetic properties, with G-GR leveraging normal gastrointestinal physiology to enhance drug absorption and effectiveness in treating postherpetic neuralgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, efficacy, and tolerability of a once-daily gastroretentive dosage form of gabapentin for the treatment of postherpetic neuralgia. Chen, C., Han, CH., Sweeney, M., et al.[2022]

In a double-blind clinical trial involving 40 children with autism, adding amantadine to risperidone significantly reduced hyperactivity and irritability compared to a placebo, indicating its potential effectiveness as an adjunct treatment.

The study found no significant difference in adverse effects between the amantadine and placebo groups, suggesting that amantadine is generally well tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, placebo-controlled trial of risperidone plus amantadine in children with autism: a 10-week randomized study. Mohammadi, MR., Yadegari, N., Hassanzadeh, E., et al.[2013]

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This trial tests whether gabapentin can improve social skills in adolescents with autism by increasing levels of a calming brain chemical called GABA.

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