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

Major Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00944996
• Other study ID #: akparl08
• Secondary ID: 920080174040-200
• Status: Completed
• Phase: N/A
• First received: July 19, 2009
• Last updated: July 25, 2012
• Start date: June 2009
• Est. completion date: July 2012

Study information

• Verified date: July 2012
• Source: Tirat Carmel Mental Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 2012
• Est. primary completion date: June 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depression

Intervention

Drug:
• SSRI; SNRI; TCA
Tablets or Pills, 1 or 2 per day, more than 2 month

Locations

Country	Name	City	State
Israel	Tirat Carmel Mental Health Center	Tirat Hacarmel

Sponsors (4)

Lead Sponsor	Collaborator
Tirat Carmel Mental Health Center	Ariel University Center of Samaria, The Nazareth Hospital, Israel, University of Michigan

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurements of PACAP and BDNF serum levels		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)	No
Primary	Analysis of genetic variants of PACAP and PAC1 coding and regulatory regions		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)	No