Major DepressionNCT00944996
Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression
A study testing SSRI; SNRI; TCA in people with Major Depression, run by Tirat Carmel Mental Health Center at 1 site in Israel.
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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depression
- What is being tested?
- SSRI; SNRI; TCA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2009to Jul 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- MDD with Co-morbidity
- Alcohol and drug use less than 1 month before the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Major Depression
- Being tested
- SSRI; SNRI; TCA
- 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
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SSRI; SNRI; TCADrug
Also called paroxetine, fluoxetine, sertraline, escitalopram, citalopram, mirtrazapine, venlafaxine, anafranil
Tablets or Pills, 1 or 2 per day, more than 2 month
| Study group | Role | What they receive |
|---|---|---|
| antidepressant | Active comparator | Not described Receives: Drug: SSRI; SNRI; TCA |
| Healthy volunteers | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurements of PACAP and BDNF serum levels
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2009 (estimated)
- Study startJun 2009
- Primary completionJun 2010
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tirat Carmel Mental Health Center
- Sponsor type
- Other government
- Collaborators
- University of Michigan, Ariel University, The Nazareth Hospital, Israel
- Responsible party
- Principal investigator, Anatoly Dr. Kreinin, Tirat Carmel Mental Health Center
- Investigators
- Anatoly Kreinin, MD, PhD, Study chair, The Bruce and Ruth Rappaport Faculty of Medicine, Technion, HaifaAlbert Pinhasov, PhD, Principal investigator, Department of Molecular Biology at Ariel University CenterLeon Raskin, PhD, Principal investigator, University of MichiganKamal Farhat, MD, Principal investigator, The Nazareth Hospital-EMMSJoseph Farah, MD, Principal investigator, The Nazareth Hospital-EMMSKlaudia Rybalksy, MD, Principal investigator, The Nazareth Hospital-EMMS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00944996
- Sponsor's protocol ID
- akparl08
- Other IDs
- 920080174, 040-2008
- Status last verified
- Jul 2012
- First submitted
- 19 Jul 2009
- Last updated
- 26 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of PACAP-BDNF Signaling System Involvement in Etiology and Treatment of Major Depression
- ClinicalTrials.gov ID
- NCT00944996
- Acronym / sponsor ID
- akparl08
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Tirat Carmel Mental Health CenterOther government
- Collaborators
- University of Michigan, Ariel University, The Nazareth Hospital, Israel
- Study start
- Jun 2009
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 23 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| antidepressant | Active comparator | Drug: SSRI; SNRI; TCA |
| Healthy volunteers | No intervention | – |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- MDD with Co-morbidity
- Alcohol and drug use less than 1 month before the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SSRI; SNRI; TCAAlso: paroxetine, fluoxetine, sertraline, escitalopram, citalopram, mirtrazapine, venlafaxine, anafranilTablets or Pills, 1 or 2 per day, more than 2 month | Drug | antidepressant |
Primary outcome
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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anatoly Kreinin, MD, PhD study chair
The Bruce and Ruth Rappaport Faculty of Medicine, Technion, Haifa
Albert Pinhasov, PhD principal investigator
Department of Molecular Biology at Ariel University Center
Leon Raskin, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SSRI; SNRI; TCA in people with Major Depression, run by Tirat Carmel Mental Health Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2012.