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

NCT00944996 | Completed DMC

• 3 other identifiers: akparl08920080174040-2008
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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)

• 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)

Study Arms (2)

antidepressant

ACTIVE COMPARATOR

Drug: SSRI; SNRI; TCA

Healthy volunteers

NO INTERVENTION

Interventions

SSRI; SNRI; TCA DRUG

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

Also known as: paroxetine, fluoxetine, sertraline, escitalopram, citalopram, mirtrazapine, venlafaxine, anafranil

antidepressant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Tirat Carmel Mental Health Center: lead
• University of Michigan: collaborator
• Ariel University: collaborator
• The Nazareth Hospital, Israel: collaborator

Study Sites (1)

Tirat Carmel Mental Health Center

Tirat Hacarmel, 30200, Israel

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Paroxetine; Fluoxetine; Sertraline; Escitalopram; Citalopram; Venlafaxine Hydrochloride; Clomipramine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propylamines; Amines; Organic Chemicals; 1-Naphthylamine; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Phenethylamines; Ethylamines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Lipids; Dibenzazepines; Heterocyclic Compounds, 3-Ring

Study Officials

• Anatoly Kreinin, MD, PhD

  The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Psychiatric Department

Study Record Dates

• First Submitted: July 19, 2009
• First Posted: July 23, 2009
• Study Start: June 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: July 1, 2012
• Last Updated: July 26, 2012

Record last verified: 2012-07

Locations

IL (1)