Diazepam Trial in GAD65 Associated Epilepsy | NCT05361447

Studies
Diazepam Trial in GAD65 Associated Epilepsy

NCT05361447

Sponsor

Mayo Clinic

Status

Withdrawn

Last Update Posted

Mar 6, 2025Actual

Enrollment

0Actual

Phase

Phase 1Phase 2

Conditions

GAD 65 Antibody-associated Epilepsy

Interventions

Diazepam

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Mar 2025

Overall Recruitment Status or Expanded Access Status

Withdrawn

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Study population was difficult to identify for enrollment interest.

Expanded Access Info

Start Date

Jan 11, 2023Actual

Primary Completion Date

Dec 13, 2024Actual

Completion Date

Dec 13, 2024Actual

First Submitted Date

May 1, 2022

First Submission Date that Met QC Criteria

May 1, 2022

First Posted Date

May 4, 2022Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Mar 4, 2025

Last Update Posted Date

Mar 6, 2025Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Yes

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief Summary

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

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

0Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GAD65 Associated Epilepsy	Experimental	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Diazepam	Drug	5 mg twice daily oral for 1 week and then increase to 10 mg twice daily oral	GAD65 Associated Epilepsy

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Not provided

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

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.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Kelsey Smith, MD	Mayo Clinic	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic in Rochester		Rochester	Minnesota	55905	United States

Label	URL
Mayo Clinic Clinical Trials	View source

Intervention Browse Module

MeSH Terms

ID	Term
D003975	Diazepam

Ancestor Terms

ID	Term
D001570	Benzodiazepinones
D001569	Benzodiazepines
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring

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