- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06063369
PEA vs. Placebo for Major Depression (PEA-01)
Palmitoylethanolamide (PEA) vs Placebo for Major Depression: a Phase II Exploratory Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a multi-center, 6-week, randomized, double blind, placebo-controlled clinical trial of PEA vs. placebo in patients with unipolar or bipolar disorder who are currently in a Major Depressive Episode (MDE). PEA or placebo will be administered as monotherapy and any antidepressant, mood stabilizer or antipsychotic medication will be tapered down starting from the randomization day. The tapering process will be of one week, except for fluoxetine which will be tapered for a duration of two weeks.
At the screening visit, after signing the informed consent form, patients will be assessed using the MINI. MADRS and YMRS will be assessed for inclusion/exclusion criteria. Demographic information will be collected, psychiatric and medical history obtained, physical examination including height and weight, blood pressure and pulse rate will be performed. Blood samples for biochemistry analyses and CBC, and urine samples for urinalysis will be taken. Females of child-bearing potential will be tested for pregnancy. An ECG will be performed. Blood for neurosteroids and other biomarkers will be taken, processed to separate plasma from PBMC and stored, to be sent later to the laboratory of Dr. Pinna.
The baseline visit will be performed up to 7 days after screening. MADRS, CGI-BP/CGI-D, HAM-A and HAM-D will be collected. The use of concomitant medications as well as Adverse Events will be recorded throughout the study. Patients will be randomized to start study medication. The clinical questionnaires will be administered 2, 4 and 6 (End-of study, EOS) weeks after baseline. Biomarker analyses, including plasma neurosteroid and BDNF levels will be measured at baseline, and at the week 6 (EOS) visit. Concomitant medications and adverse events, as well as any other clinical change will be monitored through phone visits which will take place twice weekly on weeks 1, 3 and 5.
Study medication will be manufactured by Innexus Nutraceuticals in the Netherlands according to GMP, and will then be sent to Micronisierungs-Kontor Oberrot GmbH in Germany for micronization. The micronized compound will then be sent to PharmaMed Inc. in Pennsylvania, USA for packaging and labelling. Study medication will be randomized according to a computerized list supplied by the investigators to Innexus Nutraceuticals and PharmaMed Inc. Randomization of patients will be sequential. Kits will be kept in one central site, and after randomization patients from other site will be supplied with the kits.
Concomitant medication: After the screening visit, patients will start a tapering process for all antidepressant/antipsychotic/mood stabilizer. The tapering process will be of one week, except for fluoxetine which will be tapered for a duration of two weeks.
Rescue Medication: Up to 3 mg/day of lorazepam will be allowed as rescue medication in case of clinical deterioration, based on clinician's judgment.
Laboratory: Quantification of Allo and congeners, and PEA will performed by the state-of-the-art technology, GC-MS. The methodology to determine neurosteroid levels is a technique developed in Dr Pinna's lab (HPLC combined with GC-MS quantification), which allows the simultaneous determination of various neurosteroids from a single sample due to molar sensitivity and unsurpassed structural specificity.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Igor Nastas, Dr
- Phone Number: +37367133770
- Email: igornastas@yahoo.com
Study Contact Backup
- Name: Mark Prof Weiser, Professor
- Phone Number: 972-526666570
- Email: Mark.weiser@sheba.health.gov.il
Study Locations
-
-
-
Chișinău, Moldova, Republic of
- Recruiting
- State University of Medicine and Pharmacy " Nicolae Testemitsanu"
-
Contact:
- Igor Nastas, Dr
- Phone Number: +37367133770
- Email: igornastas@yahoo.com
-
Principal Investigator:
- Mark Weiser, Professsor
-
Principal Investigator:
- Igor Nastas, Doctor
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Meet DSM V criteria for a Major Depressive Episode, with or without a diagnosis of Bipolar I or Bipolar II disorder.
- Between 18-65 years of age, male or female subjects of any race.
- Able to provide informed consent. All participant patients must have signed an informed consent document indicating they understand the purpose of the study and are willing to complying with the study procedures and restrictions.
- Have a MADRS above 20 and an YMRS < 12.
- Inpatients or outpatients at the discretion of the investigator.
- Live with a caregiver or have a relative/close friend who is in contact with them at least twice a week via phone.
Exclusion Criteria:
- Diagnosis of schizophrenia or schizoaffective disorder
- Women of child-bearing potential who do not practice contraception.
- Women who are pregnant or breast-feeding.
- Psychotic symptoms during the 2 weeks preceding the baseline day.
- Failure of three or more antidepressant treatment trials.
- Unstable medical disease (malignancy, poorly controlled diabetes, or cardiomyopathy, serious pulmonary disease, kidney disease, impaired liver functioning. Particular attention should be given to exclude patients with ischemic heart disease).
- Has a clinically significant abnormal 12-lead electrocardiogram (ECG) at the Screening Visit, as determined by the Investigator.
- At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
- Patients with a current DSM-V substance or alcohol dependence.
- Concurrent delirium, mental retardation, drug-induced psychosis.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Palmitoylethanolamide 1200 mg
Dose: PEA 1200 mg given in 300 mg capsules (2 capsules twice daily) Route of administration: oral Duration and frequency: study medication will be provided to patients in bottles every two weeks for the duration of the study (three dispensations). Formulation: PEA Dosing scheme: Patients will be instructed to take two capsules twice daily for the 42 days of the study. |
Dose: PEA 1200 mg given in 400 mg capsules (3 capsules per day) or Placebo Route of administration: oral Duration and frequency: study medication will be provided to patients in bottles every two weeks for the duration of the study (three dispensations). Formulation: PEA and placebo in identical capsules. Dosing scheme: Patients will be instructed to take two capsules twice daily for the 42 days of the study.
Other Names:
|
Placebo Comparator: Matching placebo
2 capsules twice daily identical to study arm. Route of administration: oral Duration and frequency: pills will be provided to patients in bottles every two weeks for the duration of the study (three dispensations). Formulation: placebo in identical capsules. Dosing scheme: Patients will be instructed to take two capsules twice daily for the 42 days of the study. |
Dose: PEA 1200 mg given in 400 mg capsules (3 capsules per day) or Placebo Route of administration: oral Duration and frequency: study medication will be provided to patients in bottles every two weeks for the duration of the study (three dispensations). Formulation: PEA and placebo in identical capsules. Dosing scheme: Patients will be instructed to take two capsules twice daily for the 42 days of the study.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hamilton Depression Rating Scale (HAM-D)
Time Frame: 6 weeks trial
|
Depression Scale
|
6 weeks trial
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Global Impressions-Severity-Bipolar Scale or Clinical Global Impressions-Severity-Depression
Time Frame: 6 weeks trial
|
Scale for Overall Bipolar Depression and Unipolar Depression severity
|
6 weeks trial
|
Hamilton Anxiety Rating Scale (HAM-A)
Time Frame: 6 weeks trial
|
Anxiety Scake
|
6 weeks trial
|
Plasma measures including Allo and pregnanolone, their isomers, the sulfated congeners (pregnanolone sulphate and Allo sulphate)
Time Frame: 6 weeks trial
|
neurosteroids
|
6 weeks trial
|
DHEA
Time Frame: 6 weeks trial
|
measured with the state-of-the-art methodology gas chromatography mass spectrometry (GC-MS).
|
6 weeks trial
|
BDNF
Time Frame: 6 weeks trial
|
Brain-derived neurotrophic factor
|
6 weeks trial
|
CRP
Time Frame: 6 weeks trial
|
C-Reactive Protein
|
6 weeks trial
|
TLR-4
Time Frame: 6 weeks trial
|
Toll-like Receptor 4
|
6 weeks trial
|
Cytokines
Time Frame: 6 weeks trial
|
Inflammatory markers
|
6 weeks trial
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Bipolar and Related Disorders
- Depression
- Depressive Disorder
- Bipolar Disorder
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cannabinoid Receptor Agonists
- Cannabinoid Receptor Modulators
- Palmidrol
Other Study ID Numbers
- PEA-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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