The Effect of Plasma Osmolality on Brain Glutamate (MRS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Handan Gunduz-Bruce, Yale University
ClinicalTrials.gov Identifier:
NCT00611741
First received: January 29, 2008
Last updated: August 23, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: furosemide, Na supplements
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: The Role of Cortical Glutamate and GABA in Brains Osmotic Regulation: A Pilot Study in Healthy Volunteers and in Patients With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Cortical glutamate concentration [ Time Frame: Baseline and endpoint ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cognitive function [ Time Frame: Baseline and end point ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: March 2007
Study Completion Date: March 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug intervention, longitudinal
Furosemide and Na supplements
Drug: furosemide, Na supplements
furosemide 20 mg, Na supplements 8g in divided doses/day for 5 days

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00611741

Locations
United States, Connecticut
34 Park Street, CMHC
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Handan Gunduz-Bruce, M.D. Yale School of Medicine
  More Information

No publications provided

Responsible Party: Handan Gunduz-Bruce, Assistant Clinical Professor, Yale University
ClinicalTrials.gov Identifier: NCT00611741     History of Changes
Other Study ID Numbers: 0612002149
Study First Received: January 29, 2008
Last Updated: August 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
MRS, glutamate, osmolality

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Furosemide
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014