Diazepam Trial in GAD65 Associated Epilepsy

March 4, 2025 updated by: Kelsey M. Smith, Mayo Clinic

Open Label Single Center Trial Evaluating the Efficacy and Safety of Diazepam in GAD65 Associated Epilepsy

The purpose of this study is to determine whether diazepam reduces the frequency of seizures in GAD65 antibody associated epilepsy.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

GAD65 is an intracellular enzyme that plays a key role in the conversion of glutamate to gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the CNS. Benzodiazepines augment the sensitivity of the GABA-A receptor to GABA, prolonging its inhibitory effect, perhaps enhancing the potential for neural inhibition in conditions in which GABA is depleted.

GAD65 antibodies have been identified in a subset of patients with drug resistant focal epilepsy and limbic encephalitis. While it has not been definitively determined that these antibodies cause GAD65 inhibition and GABA depletion directly, diazepam, a common benzodiazepine, has been established as a mainstay of therapy for stiffperson's syndrome, a condition that is commonly associated with GAD65 antibody positivity. Given these observations, diazepam has been used by the investigators in a small number of patients with intractable epilepsy in the setting of GAD65 antibody positivity, with some encouraging anecdotal results with one patient being rendered seizure free for three years.

The purpose of this study is to generate prospective data on use of diazepam in patients with epilepsy related to high-titer GAD65 antibody positivity.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • High-titer serum GAD65 positivity > 20 nmol/L High-titer serum GAD65 IgG seropositivity titer >20 nmol/L and/or CSF GAD65 seropositivity titer > 0.02 nmol/L.
  • Drug-resistant focal epilepsy, having failed 2 previous anti-seizure medications.
  • Stable treatment for the 1 month prior to enrollment.
  • Patients must be able to give informed consent or have an appropriate representative available to do.

Exclusion Criteria:

  • Alternative etiology for epilepsy.
  • Already on another benzodiazepine.
  • On a regularly scheduled opiate.
  • Co-existing antibodies associated with seizures.
  • Pregnancy or breast feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GAD65 Associated Epilepsy
Subjects diagnosed with GAD65 associated epilepsy, serum high-titer GAD65 positivity, trialed and failed at least 2 anti-seizure medications, at least 4 seizures per month will be started on diazepam.
Drug: Diazepam
5 mg twice daily oral for 1 week and then increase to 10 mg twice daily oral
Other Names:
  • Valium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in seizure frequency
Time Frame: Baseline, 3 months
Median percentage change in the mean monthly frequency of seizures as measured by patient recorded seizure frequency
Baseline, 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Kelsey Smith, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 11, 2023

Primary Completion (Actual)

December 13, 2024

Study Completion (Actual)

December 13, 2024

Study Registration Dates

First Submitted

May 1, 2022

First Submitted That Met QC Criteria

May 1, 2022

First Posted (Actual)

May 4, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 4, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-007195

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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