The Effect of Plasma Osmolality on Brain Glutamate (MRS)

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 Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: furosemide, Na supplements

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • 34 Park Street, CMHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cortical glutamate concentration	Baseline and endpoint

Secondary Outcome Measures

Outcome Measure	Time Frame
Cognitive function	Baseline and end point

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Handan Gunduz-Bruce, M.D., Yale School of Medicine

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: January 29, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (Estimate): February 11, 2008

Study Record Updates

• Last Update Posted (Estimate): February 9, 2016
• Last Update Submitted That Met QC Criteria: February 6, 2016
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: MRS, glutamate, osmolality
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 0612002149