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Diazepam Trial in GAD65 Associated Epilepsy

Sponsor
Mayo Clinic (Other)
Overall Status
Enrolling by invitation
CT.gov ID
NCT05361447
Collaborator
(none)
30
Enrollment
1
Location
1
Arm
16
Anticipated Duration (Months)
1.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open Label Single Center Trial Evaluating the Efficacy and Safety of Diazepam in GAD65 Associated Epilepsy
Anticipated Study Start Date :
Aug 1, 2022
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in seizure frequency [Baseline, 3 months]

      Median percentage change in the mean monthly frequency of seizures as measured by patient recorded seizure frequency

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Rochester Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic

    Investigators

    • Principal Investigator: Jeffrey Britton, MD, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Jeffrey Britton, Principal Investigator, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT05361447
    Other Study ID Numbers:
    • 21-007195
    First Posted:
    May 4, 2022
    Last Update Posted:
    Jul 22, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Epilepsy
    Diazepam

    Study Results

    No Results Posted as of Jul 22, 2022