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

July 25, 2012 updated by: Anatoly Dr. Kreinin, Tirat Carmel Mental Health Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • 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

      • Tirat Hacarmel, Israel, 30200
        • Tirat Carmel Mental Health Center

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

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

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: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: antidepressant
Tablets or Pills, 1 or 2 per day, more than 2 month
Other Names:
  • paroxetine, fluoxetine, sertraline, escitalopram, citalopram
  • mirtrazapine, venlafaxine
  • anafranil
NO_INTERVENTION: Healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
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)
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)
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)

Collaborators and Investigators

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

Investigators

  • Study Chair: Anatoly Kreinin, MD, PhD, The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa
  • Principal Investigator: Albert Pinhasov, PhD, Department of Molecular Biology at Ariel University Center
  • Principal Investigator: Leon Raskin, PhD, University of Michigan
  • Principal Investigator: Kamal Farhat, MD, The Nazareth Hospital-EMMS
  • Principal Investigator: Joseph Farah, MD, The Nazareth Hospital-EMMS
  • Principal Investigator: Klaudia Rybalksy, MD, The Nazareth Hospital-EMMS

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

June 1, 2009

Primary Completion (ACTUAL)

June 1, 2010

Study Completion (ACTUAL)

July 1, 2012

Study Registration Dates

First Submitted

July 19, 2009

First Submitted That Met QC Criteria

July 22, 2009

First Posted (ESTIMATE)

July 23, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

July 26, 2012

Last Update Submitted That Met QC Criteria

July 25, 2012

Last Verified

July 1, 2012

More Information

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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