Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy

NCT00610532 | Terminated Phase 4 Results

• 1 other identifier: 2005H0170
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The study is being done to understand why some patients with epilepsy (disease of recurrence of seizures) do not respond very well to drug treatment with anticonvulsants. Despite the availability of many anticonvulsants, about 30% of patients with epilepsy are resistant to them. The cause of the resistance is not clear, but one of the reasons could be an increased amount of proteins in the cells of the body called transporter proteins. Transporter proteins are a group of proteins that help to defend the body against toxins, including drugs, by pumping them out of the cells. Studies have shown that the number of transporter proteins is higher in the parts of the brain that trigger seizures when compared to other parts of the brain. Studies in animals have shown that taking an anticonvulsant with an inhibitor (meaning "to stop" or "to reduce") of a transporter protein can increase the concentration of that anticonvulsant inside the brain cells. The main purpose of the study is to determine if taking an anticonvulsant and a transporter protein inhibitor will change the brain concentration of the anticonvulsant. In this study, a single dose of phenytoin (Dilantin® is a brand name anticonvulsant which has phenytoin as its active ingredient), a commonly used anticonvulsant, will be given once by itself, and then will be given a separate time with a single (i.e. one time only) dose of probenecid. Probenecid, a medicine used commonly to treat gout (a disease of increased uric acid), is known to be an inhibitor of transporter proteins. The study will use electroencephalogram or EEG (recording of brain wave activities) to determine if the EEG pattern when probenecid is given, will be different from the EEG pattern when phenytoin is given alone. This will suggest that probenecid has affected the brain concentration of phenytoin.

Conditions

Epilepsy

Keywords

pharmacoresistance; healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Quantitative EEG Recordings

  end of each treatment

Study Arms (2)

A

EXPERIMENTAL

intravenous phenytoin alone

Drug: phenytoin

B

EXPERIMENTAL

intravenous phenytoin plus probenecid

Drug: phenytoin and probenecid

Interventions

phenytoin DRUG

intravenous phenytoin (15 mg/kg) single dose

A

phenytoin and probenecid DRUG

intravenous phenytoin (15 mg/kg) single dose and oral probenecid 2000 mg single dose

B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men with pharmacoresistant partial epilepsy defined as failure of two or more AEDs at a reasonable therapeutic dose
• Patient is able to understand and sign a consent form and able to keep a seizure calendar
• Patient is older than 18 years of age
• Patient is otherwise healthy by laboratory and physical examination

You may not qualify if:

• Patient is currently taking phenytoin
• Patient has a history of an adverse reaction to phenytoin
• Patient has a history of gout disease, peptic ulcer disease, blood dyscrasias, or uric acid kidney stones
• Patient has an allergy to sulfa drugs or probenecid
• Patient has been exposed to probenecid or another known transporter inhibitor (verapamil, progesterone, etc) in the three months prior to enrollment
• Patient has a history of renal impairment (creatinine clearance \< 50 ml/min)
• Patient has a history of diabetes and is taking oral sulfonylurea agents

Sponsors & Collaborators

• Jim McAuley: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Epilepsy

Interventions

Phenytoin; Probenecid

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Limitations and Caveats

problems with measurement led to uninterpretable data

Results Point of Contact

• Title: Dr. Jim McAuley
• Organization: The Ohio State University

mcauley.5@osu.edu

614-292-9713

Study Officials

• James W McAuley, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Bassel F Shneker, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 28, 2008
• First Posted: February 8, 2008
• Study Start: March 1, 2006
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: May 14, 2013
• Results First Posted: May 14, 2013

Record last verified: 2013-05

Locations

US (1)