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

Trial Summary

What is the purpose of this trial?

This trial tests whether gabapentin can improve social skills in adolescents with autism by increasing levels of a calming brain chemical called GABA. The study involves 40 adolescents and aims to see if this treatment can correct brain chemical imbalances and improve social interactions.

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 data supports the idea that Gabapentin for Autism is an effective treatment?

The available research does not provide specific data supporting the effectiveness of Gabapentin for treating autism. Instead, it discusses other drugs like risperidone and haloperidol, which have shown some positive effects on symptoms associated with autism. However, these drugs can have significant side effects. Overall, there is no consensus or strong evidence from controlled studies validating the effectiveness of Gabapentin or other drugs specifically for autism. ^{1 2 3 4 5}

What safety data exists for gabapentin treatment?

Gabapentin has been studied for safety in various contexts, primarily as an add-on therapy for partial seizures. Common adverse effects include somnolence, dizziness, and fatigue. In clinical trials, adverse events were reported in 69% of patients taking 900 mg/day and 64% taking 1,200 mg/day, compared to 52% in the placebo group. No significant hepatic or hematopoietic effects were observed. Additionally, there are reports of hypoglycemia as a potential adverse effect, particularly in patients with diabetes or on dialysis. ^{6 7 8 9 10}

Is gabapentin generally safe for humans?

Gabapentin has been studied for safety in people with seizures and other conditions. Common side effects include sleepiness, dizziness, and tiredness. Some reports mention low blood sugar in certain patients, but no major liver or blood-related issues were found in clinical studies. ^{6 7 8 9 10}

Is the drug Gabapentin promising for treating autism?

The research articles mainly discuss Gabapentin as a drug for epilepsy and pain management, not autism. They highlight its effectiveness in treating seizures and certain types of pain, but do not provide evidence or claims about its use for autism. Therefore, based on the available information, Gabapentin is not shown to be a promising treatment for autism. ^{11 12 13 14 15}

How is the drug Gabapentin unique for treating autism?

Gabapentin is unique because it is primarily used as an anti-epileptic drug and for treating nerve pain, but its use in autism is novel as there are no standard treatments specifically for autism. It has a low incidence of side effects and minimal drug interactions, which may make it a promising option for managing symptoms in autism. ^{11 12 13 14 15}

Research Team

David Cochran, MD

Principal Investigator

UMass Medical School

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 (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]

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]

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]

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 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]

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 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'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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapeutic management of autism. [2022]

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

Double-blind, placebo-controlled trial of risperidone plus amantadine in children with autism: a 10-week randomized study. [2013]

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

Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Review of psychopharmacological treatments in adolescents and adults with autistic disorders]. [2007]

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

Efficacy and safety of naltrexone use in pediatric patients with autistic disorder. [2013]

6. England 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. [2018]

7. United States 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. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Restoring invisible and abandoned trials of gabapentin for neuropathic pain: a clinical and methodological investigation. [2022]

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

Patient Case Report: Gabapentin-Induced Hypoglycemia. [2022]

10. United States 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. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Gabapentin--a new antiepileptic drug. [2018]

12. England pubmed.ncbi.nlm.nih.gov

A rare case of a gabapentin-induced cardiomyopathy. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Gabapentin: a unique anti-epileptic agent. [2018]

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

Pharmacokinetics, efficacy, and tolerability of a once-daily gastroretentive dosage form of gabapentin for the treatment of postherpetic neuralgia. [2022]

15. Switzerland pubmed.ncbi.nlm.nih.gov

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