GAD 65 Antibody-associated EpilepsyPhase 1/2NCT05361447
Diazepam Trial in GAD65 Associated Epilepsy
A Phase 1/2 study testing Diazepam in people with GAD 65 Antibody-associated Epilepsy, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to determine whether diazepam reduces the frequency of seizures in GAD65 antibody associated epilepsy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GAD 65 Antibody-associated Epilepsy
- What is being tested?
- Diazepam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jan 2023to 13 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Alternative etiology for epilepsy.
- Already on another benzodiazepine.
- On a regularly scheduled opiate.
- Co-existing antibodies associated with seizures.
- Pregnancy or breast feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: 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.
Read the 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.
- Conditions
- GAD 65 Antibody-associated Epilepsy
- Being tested
- Diazepam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiazepamDrug
Also called Valium
5 mg twice daily oral for 1 week and then increase to 10 mg twice daily oral
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Diazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in seizure frequency
Median percentage change in the mean monthly frequency of seizures as measured by patient recorded seizure frequency
Measured: Baseline, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2022
- Study start11 Jan 2023
- Primary completion13 Dec 2024
- Study completion13 Dec 2024
Why it stopped: Study population was difficult to identify for enrollment interest.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GAD 65 Antibody-associated EpilepsyStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kelsey M. Smith, Mayo Clinic
- Investigators
- Kelsey Smith, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05361447
- Sponsor's protocol ID
- 21-007195
- Status last verified
- Mar 2025
- First submitted
- 1 May 2022
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Single Center Trial Evaluating the Efficacy and Safety of Diazepam in GAD65 Associated Epilepsy
- ClinicalTrials.gov ID
- NCT05361447
- Acronym / sponsor ID
- 21-007195
- Conditions
- GAD 65 Antibody-associated Epilepsy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study population was difficult to identify for enrollment interest.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 11 Jan 2023 (actual)
- Primary completion
- 13 Dec 2024 (actual)
- Study completion
- 13 Dec 2024 (actual)
- First posted
- 4 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GAD65 Associated Epilepsy | Experimental | Drug: DiazepamSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- Alternative etiology for epilepsy.
- Already on another benzodiazepine.
- On a regularly scheduled opiate.
- Co-existing antibodies associated with seizures.
- Pregnancy or breast feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiazepamAlso: Valium5 mg twice daily oral for 1 week and then increase to 10 mg twice daily oral | Drug | GAD65 Associated Epilepsy |
Primary outcome
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2025.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kelsey Smith, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Diazepam in people with GAD 65 Antibody-associated Epilepsy, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in seizure frequency (time frame: Baseline, 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2025.