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Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression

Primary Purpose

Major Depression

Status

Completed

Phase

Not Applicable

Locations

Israel

Study Type

Interventional

Intervention

SSRI; SNRI; TCA

About this trial

This is an interventional basic science trial for Major Depression focused on measuring PACAP (Pituitary Adenylate Cyclase Activating Polypeptide), Major Depression, Receptors, Gene polymorphism, PACAP signaling system, Etiology of major depression, Mechanism of antidepressants action, PACAP receptors gene polymorphism, Pathogenesis of major depression, Responsiveness to the antidepressant drugs

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Men and women 18-65 age old
Patients with DSM-IV (or/and ICD-10) diagnosis MDD
Volunteers without DSM-IV (or/and ICD-10) diagnosis MDD
For patients with DSM-IV (or/and ICD-10) diagnosis MDD minimum 2 weeks free from benzodiazepines, mood stabilizers and neuroleptics.
All patients from MDD group treatment only by SSRI antidepressant medications.

Exclusion Criteria:

MDD with Co-morbidity
Alcohol and drug use less than 1 month before the study

Sites / Locations

Tirat Carmel Mental Health Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

antidepressant

Healthy volunteers

Arm Description

Outcomes

Primary Outcome Measures

Measurements of PACAP and BDNF serum levels

Analysis of genetic variants of PACAP and PAC1 coding and regulatory regions

Secondary Outcome Measures

Full Information

NCT ID

NCT00944996

First Posted

July 19, 2009

Last Updated

July 25, 2012

Sponsor

Tirat Carmel Mental Health Center

Collaborators

University of Michigan, Ariel University, The Nazareth Hospital, Israel

1. Study Identification

Unique Protocol Identification Number

NCT00944996

Brief Title

Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression

Official Title

Assessment of PACAP-BDNF Signaling System Involvement in Etiology and Treatment of Major Depression

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Completed

Study Start Date

June 2009 (undefined)

Primary Completion Date

June 2010 (Actual)

Study Completion Date

July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Tirat Carmel Mental Health Center

Collaborators

University of Michigan, Ariel University, The Nazareth Hospital, Israel

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The neuropeptide Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and its receptors PAC1 and VPAC2 are widely expressed in the nervous system. The investigators found that PACAP treatment of neuronal cell cultures increases expression of Brain Derived Neurotrophic Factor (BDNF) that plays an important role in the etiology of psychiatric disorders and action of antidepressants. For the first time, the investigators demonstrated that treatment by Paroxetine and Citalopram significantly decreases PAC1 and VPAC2 and upregulates PACAP mRNA expression, whereas Imipramine shows an opposite effect. Moreover, PACAP, PAC1 and VPAC2 expression is highly correlated with BDNF expression. Their in vivo studies show that Imipramine reduces BDNF and increases PAC1 mRNA expression in murine hippocampus, suggesting that antidepressants may affect neuronal plasticity through PACAP-BDNF interactions. Based on their observations in experimental systems, the investigators hypothesize that PACAP signaling system may be involved in the etiology of depression and mechanism of antidepressant action. The investigators will evaluate this hypothesis by examining serum PACAP levels, effect of antidepressants on PACAP levels, and gene polymorphisms of PACAP and its receptors in major depressive disorder patients. This study will enhance the investigators' understanding of PACAP's role in the etiology of depression and antidepressant treatment and will provide a basis to evaluate PACAP pathway as a potential target for diagnostics and novel antidepressants drug discovery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depression

Keywords

PACAP (Pituitary Adenylate Cyclase Activating Polypeptide), Major Depression, Receptors, Gene polymorphism, PACAP signaling system, Etiology of major depression, Mechanism of antidepressants action, PACAP receptors gene polymorphism, Pathogenesis of major depression, Responsiveness to the antidepressant drugs

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

InvestigatorOutcomes Assessor

Allocation

Non-Randomized

Enrollment

100 (Actual)

8. Arms, Groups, and Interventions

Arm Title

antidepressant

Arm Type

Active Comparator

Arm Title

Healthy volunteers

Arm Type

No Intervention

Intervention Type

Drug

Intervention Name(s)

SSRI; SNRI; TCA

Other Intervention Name(s)

paroxetine, fluoxetine, sertraline, escitalopram, citalopram, mirtrazapine, venlafaxine, anafranil

Intervention Description

Tablets or Pills, 1 or 2 per day, more than 2 month

Primary Outcome Measure Information:

Title

Measurements of PACAP and BDNF serum levels

Time Frame

Blood samples will be collected at the study base line, two and three weeks after that and at the study end point (8 weeks after study initiation)

Title

Analysis of genetic variants of PACAP and PAC1 coding and regulatory regions

Time Frame

Blood samples will be collected at the study base line, two and three weeks after that and at the study end point (8 weeks after study initiation)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men and women 18-65 age old Patients with DSM-IV (or/and ICD-10) diagnosis MDD Volunteers without DSM-IV (or/and ICD-10) diagnosis MDD For patients with DSM-IV (or/and ICD-10) diagnosis MDD minimum 2 weeks free from benzodiazepines, mood stabilizers and neuroleptics. All patients from MDD group treatment only by SSRI antidepressant medications. Exclusion Criteria: MDD with Co-morbidity Alcohol and drug use less than 1 month before the study

Overall Study Officials: