CClinicalTrials.gg
CompletedNCT02626832REGAVPUpdated Dec 10, 2015

Regulation of Arginine-vasopressin (AVP)

An interventional study of Procedural in Schizophrenia and Depression, sponsored by Yale University. Completed at 2 sites in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-12-10.

Sponsored by Yale University · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
25
Allocation
Non-randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

This study aims to develop a method for the assessment of central NMDA receptor functioning in patients with depression and schizophrenia. For this purpose a transitional approach is used based on preclinical studies that show a dose-dependent relationship between the activity of hypothalamic NMDA receptor and plasma AVP response to increasing plasma osmolality. Patients with schizophrenia, depression and healthy controls participated in this study. The Investigators found that in a subgroup of patients with schizophrenia the AVP response was low and that in a subgroup of subjects with depression the AVP response was high compared to healthy controls.

Read the detailed description

Evidence suggests that altered N-methyl-D-aspartate (NMDA) receptor activity and glutamate signaling may underlie the pathogenesis of both schizophrenia and depression at least in subgroups of patients. In schizophrenia, pharmacologic modeling, postmortem and imaging data suggest reduced NMDA signaling. In contrast, recent clinical trials demonstrating the efficacy of the NMDA antagonist ketamine in severely depressed patients suggest increased NMDA receptor signaling. The Investigators have conducted a proof of concept study to assess whether there is any in vivo evidence for an inverse association in depression and schizophrenia with respect to the NMDA receptor function. For this purpose the investigators used a translational approach, based on findings from animal studies that NMDA receptor is a key mediator of arginine-vasopressin (AVP) release into the bloodstream. Using hypertonic saline to induce AVP release, as done in animal studies, it was found that in a subgroup of depressed patients, NMDA receptor mediated AVP release was significantly increased, whereas in a subgroup of schizophrenia patients, the same response was abnormally low. Previous research has demonstrated that this response is well conserved. These findings are consistent with implicated NMDA receptor related abnormalities in depression and schizophrenia in subgroups of patients, and provide the first in vivo evidence towards this dichotomy.

02

Conditions studied

  • Schizophrenia
  • Depression

Keywords

  • vasopressin
  • AVP
  • NMDA
  • osmolality
03

In context

Diabetes Insipidus

117 studies on the registry are indexed under Diabetes Insipidus; 29 are open to participants now.

This study's enrollment of 25 is below the median of 57 across 64 interventional studies indexed under Diabetes Insipidus.

Browse Diabetes Insipidus studies →

Lead sponsor

Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.

Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

Inclusion criteria for healthy controls:

  • Ages of 18-55 years from all ethnic backgrounds.
  • Male or female.
  • Smoker or nonsmoker.
  • Written informed consent.

Exclusion criteria for healthy controls:

  • DSM-IV diagnosis of psychotic, anxiety, mood disorder.
  • History of major psychiatric disorder in first-degree relatives.
  • 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, uric acid, creatinine clearance, LFTs, TFTs, UA, Utox, Urine pregnancy test).
  • A history of cardiac disease including arrhythmias; history of syncope or unexplained loss of consciousness; history of renal stones or renal failure; history of diabetes mellitus or diabetes insipidus.
  • Subjects with hypertension (BP > 140/90).
  • Current hyponatremia.
  • Serum Ca2+ and uric acid levels that are above normal range.
  • Serum creatinine outside of normal range for age.
  • Creatinine clearance \<70 ml/min using the Cockcroft-Gault equation (Cockcroft et al 1976) [(140-age)*(weight in kg)*(.85 if female)/(72*Cr)].
  • 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 diuretics of any type, lithium, carbamazepine.
  • Current substance abuse/dependency determined by urine toxicology.
  • Current treatment with medications with psychotropic effects.
  • Current pregnancy, unsatisfactory birth control method report for females.
  • IQ \< 70 as determined by Wechsler Abbreviated Scale of Intelligence.
  • Non-English speaking.

Inclusion criteria for patients with schizophrenia:

  • Ages of 21-55 years from all ethnic backgrounds.
  • Male or female.
  • Smoker or nonsmoker.
  • Written informed consent.
  • DSM-IV diagnosis of schizophrenia or schizoaffective disorder.
  • For treated patients: The patient has been on a stable dose of antipsychotics for the past month and does not require a change of medications or dose adjustment at study entry.
  • 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.

Exclusion criteria for patients with schizophrenia

  • 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, uric acid, creatinine clearance, LFTs, TFTs, UA, Utox, Urine pregnancy test).
  • A history of cardiac disease including arrhythmias; history of syncope or unexplained loss of consciousness; history of renal stones or renal failure; history of diabetes mellitus or diabetes insipidus.
  • Serum Ca2+ and uric acid levels that are above normal range.
  • Serum creatinine outside of normal range for age.
  • Creatinine clearance \<70 ml/min using the Cockcroft-Gault equation [(140-age)*(weight in kg)*(.85 if female)/(72*Cr)].
  • Subjects with hypertension (BP > 140/90).
  • Current hyponatremia.
  • 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 diuretics of any type, lithium, carbamazepine.
  • Currently on clozapine as clozapine may interfere with brain water regulation (Leadbetter and Shutty, 1994).
  • Current substance abuse/dependency determined by urine toxicology.
  • Current pregnancy, unsatisfactory birth control method report for females.
  • IQ \< 70 as determined by Wechsler Abbreviated Scale of Intelligence.
  • Non-English speaking.

Inclusion criteria for patients with depression:

  • Ages of 21-55 years from all ethnic backgrounds.
  • Male or female.
  • Smoker or nonsmoker.
  • Written informed consent.
  • DSM-IV diagnosis of major depressive disorder, unipolar.
  • For treated patients: The patient has been on a stable dose of medications (antidepressants) for the past month and does not require a change of medications or dose adjustment at study entry.
  • 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.

Exclusion criteria for patients with depression:

  • 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, uric acid, creatinine clearance, LFTs, TFTs, UA, Utox, Urine pregnancy test).
  • A history of cardiac disease including arrhythmias; history of syncope or unexplained loss of consciousness; history of renal stones or renal failure; history of diabetes mellitus or diabetes insipidus.
  • Serum Ca2+ and uric acid levels that are above normal range.
  • Serum creatinine outside of normal range for age.
  • Creatinine clearance \<70 ml/min using the Cockcroft-Gault equation [(140-age)*(weight in kg)*(.85 if female)/(72*Cr)].
  • Subjects with hypertension (BP > 140/90).
  • Current hyponatremia.
  • 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 diuretics of any type, lithium, carbamazepine.
  • Current substance abuse/dependency determined by urine toxicology.
  • Current pregnancy, unsatisfactory birth control method report for females.
  • IQ \< 70 as determined by Wechsler Abbreviated Scale of Intelligence.
  • Non-English speaking.

Inclusion criteria for patients from the PRIME Clinic:

  • Ages of 18-40 years from all ethnic backgrounds.
  • Male or female.
  • Smoker or nonsmoker.
  • Written informed consent.

Exclusion criteria for patients from the PRIME Clinic:

  • 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, uric acid, creatinine clearance, LFTs, TFTs, UA, Utox, Urine pregnancy test).
  • A history of cardiac disease including arrhythmias; history of syncope or unexplained loss of consciousness; history of renal stones or renal failure; history of diabetes mellitus or diabetes insipidus.
  • Serum Ca2+ and uric acid levels that are above normal range.
  • Serum creatinine outside of normal range for age.
  • Creatinine clearance \<70 ml/min using the Cockcroft-Gault equation [(140-age)*(weight in kg)*(.85 if female)/(72*Cr)].
  • Subjects with hypertension (BP > 140/90).
  • Current hyponatremia.
  • 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 diuretics of any type, lithium, carbamazepine.
  • Currently on clozapine as clozapine may interfere with brain water regulation (Leadbetter and Shutty, 1994).
  • Current substance abuse/dependency determined by urine toxicology.
  • Current pregnancy, unsatisfactory birth control method report for females.
  • IQ \< 70 as determined by Wechsler Abbreviated Scale of Intelligence.
  • Non-English speaking.
05

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    Healthy Control

    This group is represented by healthy controls

    Other: Procedural

  • Experimental
    Depression

    This experimental group is represented by subjects with depression

    Other: Procedural

  • Experimental
    Schizophrenia

    This experimental group is represented by subjects with schizophrenia

    Other: Procedural

  • Experimental
    Prodromal subjects

    This experimental group is represented by subjects with prodromal symptoms for schizophrenia

    Other: Procedural

Interventions

  • OtherProcedural

    All subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations

06

What researchers measure

Primary outcomes

  1. AVP response to plasma osmolality as measured by slopes between the two variables

    Time frame: Within 3 months

07

Study locations

2 sites
  • The John Pierce Laboratory
    New Haven, Connecticut 06519, United States
  • VA Connecticut Healthcare System
    West Haven, Connecticut 06516, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 10, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02626832
Lead sponsor
Yale University
Collaborators
VA Connecticut Healthcare System, The John B. Pierce Laboratory
Responsible party
Sponsor
First posted
Dec 10, 2015
Start date
Feb 2010
Primary completion
Nov 2013
Completion
Dec 2014
Last update
Dec 10, 2015

Study contacts

Handan Gunduz-Bruce, MD, MBA
principal investigator · Yale University

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2015. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion