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

This study has been completed.
Sponsor:
Collaborators:
University of Michigan
Ariel University Center of Samaria
The Nazareth Hospital, Israel
Information provided by (Responsible Party):
Anatoly Dr. Kreinin, Tirat Carmel Mental Health Center
ClinicalTrials.gov Identifier:
NCT00944996
First received: July 19, 2009
Last updated: July 25, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention
Major Depression
Drug: SSRI; SNRI; TCA

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Assessment of PACAP-BDNF Signaling System Involvement in Etiology and Treatment of Major Depression

Resource links provided by NLM:


Further study details as provided by Tirat Carmel Mental Health Center:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: June 2009
Study Completion Date: July 2012
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: antidepressant Drug: SSRI; SNRI; TCA
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00944996

Locations
Israel
Tirat Carmel Mental Health Center
Tirat Hacarmel, Israel, 30200
Sponsors and Collaborators
Tirat Carmel Mental Health Center
University of Michigan
Ariel University Center of Samaria
The Nazareth Hospital, Israel
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
  More Information

No publications provided

Responsible Party: Anatoly Dr. Kreinin, Director of Psychiatric Department, Tirat Carmel Mental Health Center
ClinicalTrials.gov Identifier: NCT00944996     History of Changes
Other Study ID Numbers: akparl08, 920080174, 040-2008
Study First Received: July 19, 2009
Last Updated: July 25, 2012
Health Authority: Israel: Ministry of Health

Keywords provided by Tirat Carmel Mental Health Center:
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

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Pituitary Adenylate Cyclase-Activating Polypeptide
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Growth Substances
Physiological Effects of Drugs
Vasodilator Agents
Cardiovascular Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014