Regulation of Arginine-vasopressin (AVP) (REGAVP)

December 8, 2015 updated by: Yale University

Regulation of Arginine-vasopressin (AVP) in Psychiatric Disorders

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Healthy Control
This group is represented by healthy controls
Other: Procedural
All subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations
Experimental: Depression
This experimental group is represented by subjects with depression
Other: Procedural
All subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations
Experimental: Schizophrenia
This experimental group is represented by subjects with schizophrenia
Other: Procedural
All subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations
Experimental: Prodromal subjects
This experimental group is represented by subjects with prodromal symptoms for schizophrenia
Other: Procedural
All subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
AVP response to plasma osmolality as measured by slopes between the two variables
Time Frame: Within 3 months
Within 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
VA Connecticut Healthcare System
The John B. Pierce Laboratory

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Handan Gunduz-Bruce, MD, MBA, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 10, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 10, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0910005875

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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