SchizophreniaREGAVPNCT02626832
Regulation of Arginine-vasopressin (AVP)
A study testing Procedural in people with Schizophrenia and Depression, run by Yale University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Depression
- What is being tested?
- Procedural
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2010to Dec 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Ages of 18-55 years from all ethnic backgrounds.
- Male or female.
- Smoker or nonsmoker.
- Written informed consent.
- Ages of 21-55 years from all ethnic backgrounds.
- Male or female.
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- 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.
- 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.
- Ages of 18-40 years from all ethnic backgrounds.
- Male or female.
- Smoker or nonsmoker.
- Written informed consent.
Who cannot join
- 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.
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- 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.
- 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.
- 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.
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The John Pierce Laboratory
New Haven, Connecticut, 06519
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
Official title: 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.
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.
- Conditions
- Schizophrenia, Depression
- Being tested
- Procedural
- Keywords
- vasopressin, AVP, NMDA, osmolality
- Medical subject headings
- Schizophrenia, Depression, Diabetes Insipidus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProceduralOther
All subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control | Experimental | This group is represented by healthy controls Receives: Other: Procedural |
| Depression | Experimental | This experimental group is represented by subjects with depression Receives: Other: Procedural |
| Schizophrenia | Experimental | This experimental group is represented by subjects with schizophrenia Receives: Other: Procedural |
| Prodromal subjects | Experimental | This experimental group is represented by subjects with prodromal symptoms for schizophrenia Receives: Other: Procedural |
What is being measured
The primary outcome is the main question the study is designed to answer.
AVP response to plasma osmolality as measured by slopes between the two variables
Measured: Within 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2015 (estimated)
- Study startFeb 2010
- Primary completionNov 2013
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Connecticut Healthcare System, The John B. Pierce Laboratory
- Responsible party
- Sponsor
- Investigators
- Handan Gunduz-Bruce, MD, MBA, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02626832
- Sponsor's protocol ID
- 0910005875
- Acronym
- REGAVP
- Status last verified
- Dec 2015
- First submitted
- 4 Nov 2015
- Last updated
- 10 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Arginine-vasopressin (AVP) in Psychiatric Disorders
- ClinicalTrials.gov ID
- NCT02626832
- Acronym / sponsor ID
- REGAVP / 0910005875
- Conditions
- Schizophrenia, Depression
- Keywords
- vasopressin, AVP, NMDA, osmolality
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- VA Connecticut Healthcare System, The John B. Pierce Laboratory
- Study start
- Feb 2010
- Primary completion
- Nov 2013 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 10 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy Control | Experimental | Other: ProceduralThis group is represented by healthy controls |
| Depression | Experimental | Other: ProceduralThis experimental group is represented by subjects with depression |
| Schizophrenia | Experimental | Other: ProceduralThis experimental group is represented by subjects with schizophrenia |
| Prodromal subjects | Experimental | Other: ProceduralThis experimental group is represented by subjects with prodromal symptoms for schizophrenia |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- Ages of 18-55 years from all ethnic backgrounds.
- Male or female.
- Smoker or nonsmoker.
- Written informed consent.
- Ages of 21-55 years from all ethnic backgrounds.
Key exclusion criteria (53 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProceduralAll subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations | Other | Depression, Healthy Control, Prodromal subjects, Schizophrenia |
Primary outcome
AVP response to plasma osmolality as measured by slopes between the two variables
Time frame: Within 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Handan Gunduz-Bruce, MD, MBA principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Procedural in people with Schizophrenia and Depression, run by Yale University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 53 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AVP response to plasma osmolality as measured by slopes between the two variables (time frame: Within 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2015.