Pilot Study Effect of Sulfasalazine on Glutamate Levels by(Magnetic Resonance Spectroscopy)MRS in Patients With Glioma

NCT ID: NCT01577966

Last Updated: 2016-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-01-31

Brief Summary

The main purpose of this part of the study is to determine the Central Nervous System bioavailability of sulfasalazine.

Detailed Description

This is a pilot, open-label, non-randomized, study to determine the effect that orally administered sulfasalazine has on glutamate levels as measured by MRS and on epileptiform spiking as measured by simultaneous MEG/EEG. The intent of the dose escalation is to determine an Optimal Biological Dose (OBD) based on changes in tumor glutamate levels. The OBD is defined as the dose that has the maximal reduction in tumor glutamate levels after normalization to uninvolved brain.

Conditions

Brain Tumor

Keywords

Patients with brain tumors associated with seizures

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sulfasalazine

Group Type: EXPERIMENTAL

Sulfasalazine

Intervention Type: DRUG

Sulfasalazine has been the parent aminosalicylate in use for over 40 years in the treatment of inflammatory bowel disease. The drug is a conjugate of sulfapyridine linked to 5-aminosalicylic acid. In inflammatory bowel disease, the 5-ASA component is the active moiety

Sulfasalazine is a prodrug that consists of sulfapyridine bonded to mesalamine (5-ASA). Sulfasalazine is cleaved by colonic bacterial azo-reductases into sulfapyridine and the 5-ASA moiety. 5-ASA is metabolized to N-acetyl-5-ASA by an enzyme in the intestinal epithelium and the liver and then excreted in the urine as a mixture of free 5ASA and N-acetyl-5-ASA.

Interventions

Sulfasalazine

Sulfasalazine has been the parent aminosalicylate in use for over 40 years in the treatment of inflammatory bowel disease. The drug is a conjugate of sulfapyridine linked to 5-aminosalicylic acid. In inflammatory bowel disease, the 5-ASA component is the active moiety

Sulfasalazine is a prodrug that consists of sulfapyridine bonded to mesalamine (5-ASA). Sulfasalazine is cleaved by colonic bacterial azo-reductases into sulfapyridine and the 5-ASA moiety. 5-ASA is metabolized to N-acetyl-5-ASA by an enzyme in the intestinal epithelium and the liver and then excreted in the urine as a mixture of free 5ASA and N-acetyl-5-ASA.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients must be > 18 years of age or older.

2. Patients must have histologically proven low grade astrocytoma,anaplastic astrocytoma, anaplastic mixed glioma, anaplastic oligodendroglioma,glioblastoma multiforme, astrocytoma WHO II,oligodendroglioma WHO II or mixed glioma WHO II. Patients do not haveto demonstrate progressive disease to participate in this study.

3. Patients must have completed initial glioma therapy involving radiation and be 3 months from the completion of radiation therapy. If initial glioma therapy did not include radiation (example: anaplastic oligodendroglioma), then 2 cycles of chemotherapy must be completed prior to study entry.

4. Patients must be maintained on a stable corticosteroid regimen for > 5 days prior to entry.

5. Patients must have a Karnofsky performance status > 60% (i.e. the patient must be able to care for himself/herself with occasional help from others).

6. Patients must have adequate hematologic, renal and liver function (i.e. Absolute neutrophil count > 1500/mm3, Platelets > 100,000/mm3, creatinine > 1.5 mg/dl.

7. Women of childbearing potential must have a negative pregnancy test.

8. Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be harmful to the developing fetus or nursing infant. Women of child-bearing potential must agree to use adequate contraception (either surgical sterilization; approved hormonal contraceptives such as birth control pills: Depo-Provera, or Lupron Depot; barrier methods such as condom or diaphragm along with spermicide; or an IUD). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and study PI immediately.

9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. Pregnant or breast feeding.

2. Exclude sexually active males and females unwilling to practice contraception during the study.

3. Serious concurrent infections.

4. Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within the last 12 months.

5. Patients with other serious uncontrolled co-morbid diseases that the investigator feels may comprise the study findings.

6. Allergic or sensitivity to sulfa containing medications.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Louis Burt Nabors, MD

Professor, Neurology Chair Office

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Louis B Nabors, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

UAB 1108

Identifier Type: -

Identifier Source: org_study_id