Official Title: “The Role of Cortical Glutamate and GABA in Brains Osmotic Regulation: A Pilot Study in Healthy Volunteers and in Patients With Schizophrenia”

This study is designed to test the hypothesis that plasma osmolality is linked with cortical glutamate concentrations in the brain. It also investigates whether the glutamate response in schizophrenia is enhanced compared to healthy controls.

Study Type: Interventional

Study Design: Other, Open Label, Parallel Assignment

Study Primary Completion Date: March 2012

Intervention(s) in this Clinical Trial

• Drug: furosemide, Na supplements
  • furosemide 30 mg, Na supplements 8g in divided doses/day for 5 days

Primary Measures

• Cortical glutamate concentration
  • Time Frame: Baseline and endpoint
    Safety Issue?: No

Secondary Measures

• Cognitive function
  • Time Frame: Baseline and end point
    Safety Issue?: No

• Inclusion criteria for healthy controls
• 1. Ages of 21-45 years from all ethnic backgrounds.
• 2. Male or female.
• 3. Written informed consent.
• 4. Female subjects will be studied during the follicular phase of their menstrual cycle.*
• Exclusion criteria for healthy controls
• 1. DSM-IV diagnosis of psychotic, anxiety, mood disorder.
• 2. A history of significant medical/neurological disease. Unstable medical condition based on EKG, vital signs, physical examination and laboratory work-up (CBC with differential, SMA-7, LFTs, TFTs, UA, Utox, Urine pregnancy test, folic acid, B12 levels).
• 3. History of allergies to drugs such as sulfa, multiple adverse drug reactions or known allergy to furosemide.
• 4. Any medication that in the opinion of the PI could interfere with either the safety of the study and/or the outcome measures, such as over the counter cough suppressants or antihistamines.
• 5. History of major psychiatric disorder in first-degree relatives.
• 6. Current substance abuse/dependency determined by plasma and urine toxicology.
• 7. Current treatment with medications with psychotropic effects.
• 8. Current pregnancy, unsatisfactory birth control method report for females.
• 9. Education < 12th grade.
• 10. Non-English speaking.
• Inclusion criteria for patients with schizophrenia
• 1. Ages of 21-45 years from all ethnic backgrounds.
• 2. Male or female.
• 3. Written informed consent.
• 4. DSM-IV diagnosis of schizophrenia or schizoaffective disorder.
• 5. For treated patients: The patient has been on a stable dose of medications (antipsychotics, antidepressants) for the past month and does not require a change of medications or dose adjustment at study entry.
• 6. For untreated patients: Has refused to be treated with medications, maintains regular clinic appointments with the clinicians, and does not pose an imminent danger to himself or others.
• 7. Female subjects will be studied during the follicular phase of their menstrual cycle*.
• Exclusion criteria for patients with schizophrenia
• 1. A history of significant medical/neurological disease. Unstable medical condition based on EKG, vital signs, physical examination and laboratory work-up (CBC with differential, SMA-7, LFTs, TFTs, UA, Utox, Urine pregnancy test, folic acid, B12 levels).
• 2. Orthostatic systolic blood pressure change>20 mmHg or orthostatic pulse change>20 bpm.
• 3. History of polydipsia/hyponatremia**.
• 4. History of allergies to drugs such as sulfa, multiple adverse drug reactions or known allergy to furosemide.
• 5. Any medication that in the opinion of the PI could interfere with either the safety of the study and/or the outcome measures, such as over the counter cough suppressants or antihistamines.
• 6. Current use of lithium (lithium directly interferes with electrolyte balance).
• 7. Currently on clozapine as clozapine may interfere with brain water regulation (Leadbetter and Shutty, 1994).
• 8. Current substance abuse/dependency determined by plasma and urine toxicology.
• 9. Current treatment with benzodiazepines or mood stabilizers (these medications can alter glutamate transmission).
• 10. Current pregnancy, unsatisfactory birth control method report for females.
• 11. IQ < 70 as determined by Wechsler Abbreviated Scale of Intelligence.
• 12. Non-English speaking

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Yale University

Overall Clinical Trial Officials and Contacts

Handan Gunduz-Bruce, M.D. Principal Investigator Yale School of Medicine  

Overall Contact: Sara Thaxton, BS 203 932 5711 sara.thaxton@yale.edu

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00611741

Study ID Number: 0612002149

ClinicalTrials.gov Identifier: NCT00611741

Health Authority: United States: Institutional Review Board