- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00944996
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
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
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Tirat Hacarmel, Israel, 30200
- Tirat Carmel Mental Health Center
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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:
- 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
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 |
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ACTIVE_COMPARATOR: antidepressant
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Tablets or Pills, 1 or 2 per day, more than 2 month
Other Names:
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NO_INTERVENTION: Healthy volunteers
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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)
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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)
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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)
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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
Terms related to this study
Keywords
- Receptors
- Major Depression
- Gene polymorphism
- PACAP (Pituitary Adenylate Cyclase Activating Polypeptide)
- 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
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Depression
- Depressive Disorder
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Serotonin and Noradrenaline Reuptake Inhibitors
- Antidepressive Agents, Tricyclic
- Cytochrome P-450 CYP2D6 Inhibitors
- Sertraline
- Citalopram
- Clomipramine
- Paroxetine
- Venlafaxine Hydrochloride
- Fluoxetine
Other Study ID Numbers
- akparl08
- 920080174
- 040-2008
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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