Study of Neuroimaging Biomarkers of Social Cognition Deficits in Adolescents (Age 13-17) With Autism Spectrum Disorder and Effects of Gabapentin

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

19 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests gabapentin, a medication for nerve pain and seizures, to see if it can help adolescents with Autism Spectrum Disorder (ASD) improve their social communication skills. The study focuses on adolescents aged 13-17 because they often struggle with social communication. Gabapentin may work by increasing a calming brain chemical called GABA. Gabapentin is a newer medication used in children and has been evaluated for its effectiveness and safety in various studies.

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.

What data supports the effectiveness of the drug Gabapentin?

Gabapentin has shown effectiveness in reducing neuropathic pain, with studies indicating significant pain relief and improved quality of life compared to a placebo. It has been used successfully for pain related to nerve injuries and anticancer treatments, with many patients experiencing a notable reduction in pain intensity. ^{1 2 3 4 5}

Is gabapentin generally safe for humans?

Gabapentin is generally considered safe and well-tolerated, with common side effects including sleepiness, dizziness, and fatigue. Serious side effects are rare, and it has been used safely in various conditions like epilepsy and neuropathic pain. ^{6 7 8 9 10}

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

Gabapentin is unique because it interacts with specific calcium channels in the nervous system, which helps manage pain and seizures. Unlike many other treatments, it has minimal drug interactions and is well-tolerated, making it a versatile option for conditions like neuropathic pain and epilepsy. ^{1 11 12 13 14}

Research Team

David Cochran, MD, PhD

Principal Investigator

University of Massachusetts, Worcester

Eligibility Criteria

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

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

Treatment Details

Interventions

• Gabapentin

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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

Gabapentin--a new antiepileptic drug. [2018]

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

Gabapentin for relief of neuropathic pain related to anticancer treatment: a preliminary study. [2018]

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

Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin litigation. [2021]

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

Is there a role for combined use of gabapentin and pregabalin in pain control? Too good to be true? [2019]

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. Korea (South) 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. [2021]

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

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

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

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

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

Gabapentin as add-on therapy for refractory partial epilepsy: results of five placebo-controlled trials. [2019]

11. Denmark pubmed.ncbi.nlm.nih.gov

[Gabapentin--yet another antiepileptic agent for the treatment of neuropathic pain?]. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Gabapentin in partial epilepsy. UK Gabapentin Study Group. [2018]

14. Spain pubmed.ncbi.nlm.nih.gov

Gabapentin: a Ca2+ channel alpha 2-delta ligand far beyond epilepsy therapy. [2018]