Buspirone Therapy for Localized Epilepsy

NCT01496612 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 12003312-N-0033
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Buspirone is a drug that is approved for the treatment of anxiety in adults. Studies suggest that buspirone might act on parts of the brain that can increase certain levels of brain activity. Increasing this brain activity may help decrease epileptic seizures that come from certain parts of the brain. Researchers want to see if buspirone can reduce seizure frequency in people with seizures who are already taking antiseizure medication. Objectives: To test whether buspirone can reduce the frequency of seizures in people whose seizures seem to start from one part of the brain. Eligibility: Individuals between 18 and 65 years of age who have seizures coming from one or more places in the brain. Participants must have tried at least two different antiseizure medications. Participants must also have had at least three seizures during a 1-month observation period while on current medicines. Design: Participants will have a screening visit with a physical exam and medical history. Participants will complete mood and memory testing scales. Blood, urine, and saliva samples will be collected. Participants will have a magnetic resonance imaging scan to evaluate brain structures that relate to epilepsy. They will also have a positron emission tomography scan to look at parts of the brain that are affected by buspirone. Participants will start taking a study drug (either buspirone or placebo) twice daily. They will keep a calendar of seizures and record any side effects. Treatment will be monitored with clinic visits and blood samples. After 12 weeks on the study drug, participants will gradually stop taking either the placebo or buspirone over two weeks. They will stay off the drug for another 2 weeks. After 2 weeks, participants will start taking a study drug that is the opposite of the one they had before. They will keep a calendar of seizures and record any side effects. Treatment will be monitored with clinic visits and blood samples. After 12 weeks on the study drug, participants will gradually stop taking either the placebo or buspirone. Participants will have a final followup visit with additional blood tests, mood and memory testing scales and imaging studies.

Conditions

Anxiety Disorder; Seizures; Epilepsy; Partial Epilepsy; Depression

Keywords

Epilepsy; Temporal Lobe Epilepsy; Serotonin 1A Receptor; Seizures

Outcome Measures

Primary Outcomes (1)

• Seizure Frequency in the Buspirone (Active) and Placebo Periods

  Participants utilized a seizure calendar to record the number of seizures that occurred during the three month treatment period, i.e., while participants were either taking Buspirone or Placebo. Seizure frequency was calculated as the total number of seizures occurring during each three month period. For each period a mean was calculated across subjects.

  Three months

Secondary Outcomes (6)

• Mean Score on the Hamilton Anxiety Rating Scale (HAM-A) at the End of the Active and Placebo Periods.

  Three months

• Mean Score on the Hamilton Depression Rating Scale (HAM-D) at the End of the Active and Placebo Periods

  Three months

• Mean Score on the Beck Depression Inventory (BDI) at the End of the Active and Placebo Periods

  Three months

• Mean Score on the Cancellation Task Following 3 Months on Active Drug and 3 Months on Placebo

  Three months

• Mean Score on the Trail Making Test-A (TMT-A) Following 3 Months on Active Drug and 3 Months on Placebo

  Three months

Study Arms (2)

Study Phase

EXPERIMENTAL

Drug: Buspirone

Alternate Study Phase

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Buspirone DRUG

Study Phase

Placebo DRUG

Alternate Study Phase

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be male or female.
• Patients will be aged 18 65
• Patients must have at least 3 seizures during the one-month baseline.
• Localization-related epilepsy diagnosed by standard clinical criteria that has not responded to treatment with two standard antiepileptic drugs either sequentially or in combination.
• Patients must be able to provide informed consent
• Patients must be able to remain on their baseline AED drugs and doses throughout the study
• Patients must be able to use seizure calendars to record seizures throughout the trial.

You may not qualify if:

• Pregnant patients will not participate in the study.
• During the study, women of child-bearing potential must use a reliable method of birth control and will have pregnancy testing throughout the protocol.
• Use of any alcohol or recreational drugs starting two weeks before entering baseline and for the duration of the study.
• Patients on medications with potential for a clinically significant interaction with buspirone, including MAO inhibitors, clozapine, zolpidem, hypnotics, hydromorphone derivatives, oxycodone, and diltiazem.
• Current treatment for psychiatric disorder other than depression, anxiety or bipolar disorder.
• Patients with a diagnosis of schizophrenia.
• Current treatment for another significant medical disorder, such as diabetes, or heart disease, or an untreated disorder, that might interfere with the study.
• Calculated Creatinine clearance of less than 80 ml/min calculated with the Cockcroft-Gault formula:
• Clcr = \[(140-age) times ideal body weight in Kg\] times (0.85 if female) divided by (72 times serum Cr in mg/dL)
• Evidence of impaired liver function based on serum chemistries.
• Inability to participate in the study procedures, such as MRI, PET, seizure and adverse event recording, or drug titration

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Alper K, Schwartz KA, Kolts RL, Khan A. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry. 2007 Aug 15;62(4):345-54. doi: 10.1016/j.biopsych.2006.09.023. Epub 2007 Jan 16.

  PMID: 17223086 BACKGROUND

• Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Moshe SL, Nordli D, Plouin P, Scheffer IE. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010 Apr;51(4):676-85. doi: 10.1111/j.1528-1167.2010.02522.x. Epub 2010 Feb 26.

  PMID: 20196795 BACKGROUND

• Bhagwagar Z, Rabiner EA, Sargent PA, Grasby PM, Cowen PJ. Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Mol Psychiatry. 2004 Apr;9(4):386-92. doi: 10.1038/sj.mp.4001401.

  PMID: 15042104 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Seizures; Epilepsy; Epilepsies, Partial; Depression; Epilepsy, Temporal Lobe

Interventions

Buspirone

Condition Hierarchy (Ancestors)

Mental Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Behavioral Symptoms; Behavior; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Results Point of Contact

• Title: Dr. William Theodore
• Organization: NIH/NINDS

theodorw@ninds.nih.gov

301-496-1505

Study Officials

• William H Theodore, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2011
• First Posted: December 21, 2011
• Study Start: November 22, 2011
• Primary Completion: April 19, 2016
• Study Completion: April 19, 2016
• Last Updated: October 5, 2021
• Results First Posted: September 5, 2021

Record last verified: 2016-04-19

Locations

US (1)