Gabapentin for Autism

Overseen By Arline Mata, BA

Age: < 18

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Massachusetts, Worcester

Must not be taking: Opioids, Benzodiazepines, Gabapentin

Disqualifiers: Neurological, Genetic, Psychiatric, Substance use, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how gabapentin can assist with social communication challenges in adolescents with Autism Spectrum Disorder (ASD). Researchers are examining the brain's chemical balance, focusing on neurotransmitters like GABA, which may influence social difficulties. Participants will receive a single dose of gabapentin, and brain imaging will measure any changes. Teens aged 13-17 with an ASD diagnosis who primarily communicate in English may qualify to join. As an Early Phase 1 trial, this research seeks to understand how gabapentin works in people, offering participants a chance to contribute to groundbreaking insights.

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 (like opioids or benzodiazepines) or if you are already on gabapentin.

Is there any evidence suggesting that gabapentin is likely to be safe for humans?

Research has shown that gabapentin is generally well-tolerated. Studies have found that while some people may experience side effects, these are usually mild and temporary. Common side effects include dizziness or sleepiness. It is important to note that gabapentin, like other similar medications, has been linked to an increased risk of suicidal thoughts, though this risk is similar across many drugs of this type. Gabapentin already has FDA approval for other uses, indicating its safety when used as directed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autism?

Gabapentin is unique because it targets social cognition deficits in adolescents with Autism Spectrum Disorder, an area not specifically addressed by current treatments like behavioral therapy and antipsychotic medications. While most treatments focus on behavior management or reducing irritability, gabapentin works by modulating neurotransmitter activity in the brain, potentially improving social interaction skills. Researchers are excited about gabapentin's ability to show changes in neuroimaging markers quickly, offering a new avenue for enhancing social cognition in this population.

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

Research has shown that gabapentin might increase a brain chemical called GABA, which plays a role in understanding and interacting with others. Studies have found that gabapentin can alter brain activity by boosting signals in specific areas. For instance, one study discovered that a single dose of gabapentin changed brain activity related to GABA in healthy adults. In this trial, participants will receive a single dose of gabapentin, and researchers will measure neuroimaging markers before and after administration to assess its effects. These findings suggest that gabapentin might help balance brain chemicals involved in social challenges seen in autism. Although it's still early, the evidence provides a promising hint that gabapentin could improve social skills by affecting brain chemistry. ^{6 7 8 9 10}

Who Is on the Research Team?

David Cochran, MD, PhD

Principal Investigator

University of Massachusetts, Worcester

Are You a Good Fit for This Trial?

Inclusion Criteria

Individuals who score above 70 on the Weschler Abbreviated Scale of Intelligence are considered to be highly intelligent.

The guardian must be informed of the study and must also agree to it in writing.

Age 13-17 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial 1H-MRS study to measure baseline GABA levels in the anterior cingulate cortex and occipital cortex

1 day

1 visit (in-person)

Treatment

Single dose of gabapentin 900 mg administered, followed by repeated 1H-MRS to measure changes in GABA levels

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gabapentin

How Is the Trial Designed?

Group I: Gabapentin Experimental Treatment 1 Intervention

Single dose of gabapentin 900 mg will be given and neuroimaging markers will be measured before and after administration of 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?

University of Massachusetts, Worcester

Lead Sponsor

Trials

372

Recruited

998,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

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]

In a study involving outpatients with various neuropathic pain syndromes, administering gabapentin in four different doses (QID) significantly reduced average daily pain scores and sleep disturbances compared to a three-times-daily dosing method (TID).

The QID dosing method also led to fewer adverse effects, although it did not significantly change the frequency, severity, or duration of breakthrough pain compared to the TID method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of four different doses of gabapentin reduces awakening from breakthrough pain and adverse effects in outpatients with neuropathic pain during the initial titration. Yang, JY., Lee, WI., Shin, WK., et al.[2021]

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, while commonly prescribed for pain and epilepsy, has been associated with impaired driving in 137 cases studied, with a mean blood concentration of 8.4 mg/L, indicating potential risks for users.

In most cases (93%), gabapentin was found alongside other drugs, and even when it was the only drug detected, it caused symptoms that could mimic central nervous system depressants, complicating the assessment of impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of gabapentin in impaired driving cases in Washington State in 2003-2007. Peterson, BL.[2019]

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]

In a study involving 120 patients with neuropathic pain from nerve injury, gabapentin showed significant pain relief compared to placebo, with a notable reduction in pain interference with sleep.

While there was no significant difference in the primary pain intensity score, both patients and clinicians reported better overall improvement with gabapentin, and it was well tolerated with common side effects being dizziness and tiredness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study. Gordh, TE., Stubhaug, A., Jensen, TS., et al.[2021]

Gabapentin and pregabalin, both used for neuropathic pain, can be combined effectively without significant drug interactions, potentially enhancing pain control while allowing for lower doses of each medication.

This combination therapy may help reduce side effects and improve therapeutic responses, but careful consideration of pharmacokinetics and patient tolerance is necessary before recommending it as a first-line treatment for difficult pain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for combined use of gabapentin and pregabalin in pain control? Too good to be true? Senderovich, H., Jeyapragasan, G.[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]

Citations

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Gabapentin evoked changes in functional activity in ... Results: Random effect analysis revealed that the lower dose of GBP produced significant (P<0.001) increases in BOLD signal intensity in several brain regions, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05063656

Study Details | NCT05063656 | Biomarker-Driven ... A secondary outcome will be the clinical effects of gabapentin on social cognition. This study can demonstrate for the first time that neuroimaging biomarkers ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK564186/

Results of the mechanistic substudy - Gabapentin ... Neuroimaging work in healthy humans has found that a single 1800-mg dose of gabapentin during experimentally-induced central sensitisation reduced both PAG ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666956021000015

Acute gabapentin administration in healthy adults. A ... Multimodal neuroimaging approaches have provided compelling evidence that alterations in GABAergic signalling are prevalent in a range of neuropsychiatric and ...

5. bmjopen.bmj.com bmjopen.bmj.com/content/9/6/e026152

The use of brain functional magnetic resonance imaging to ... A pilot exploratory study to determine the feasibility of investigating the mechanism of action of gabapentin in managing women with CPP using brain fMRI.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/020235s064_020882s047_021129s046lbl.pdf

NEURONTIN (gabapentin) - accessdata.fda.gov The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying ...

7. pfe-pfizercom-prod.s3.amazonaws.com pfe-pfizercom-prod.s3.amazonaws.com/products/material_safety_data/gabapentin_tablets_8-Nov-2018.pdf

SAFETY DATA SHEET Signal Word: Not required. Hazard Statements: Non-hazardous in accordance with international standards for workplace safety. Other Hazards. An ...

8. sigmaaldrich.com sigmaaldrich.com/US/en/sds/SIGMA/G154?srsltid=AfmBOoq-Cph6P0neHnvVPRpuuTBE8Rg1ImXniEP1l4yDJDAEcvFjLPQI

SAFETY DATA SHEET OSHA: No component of this product present at levels greater than or equal to 0.1% is on OSHA's list of regulated carcinogens. Reproductive ...

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Gabapentin (oral route) - Side effects & dosage However, safety and efficacy have not been established in children younger than 3 years of age. Appropriate studies have not been performed on ...

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Clinical efficacy and safety of gabapentin Gabapentin is well tolerated. Although adverse events occur in most patients receiving gabapentin as adjunctive therapy, they are transient and mild to moderate ...