PET-MRI F-DOPA Activity in the Mesocorticolimbic System and Depressive Symptoms in the Prediction of Treatment Compatibility

NCT03026309 | Unknown

• 1 other identifier: 0112-16-ASMC
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Main objectives: Comparing levels of F-DOPA reuptake rate as an indicator for Dopamine metabolism of un-medicated Depressed patients to healthy individuals in the Mesocorticolimbic System (VTA-NAc-PFC) and assessing structural differences between the two groups in the Hippocampus, Hypothalamic-Pituitary gland and Mesocorticolimbic System (VTA-NAc-PFC) and resting state fMRI. Secondary objectives: 1. Comparing the differences of DNA Methylation in the plasma and serum of patients compared to healthy controls. 2.Assessing the correlation between symptoms' severity score (evaluated based on Hamilton Rating Scale) at base line and 6 months following treatmnt to PET 18F-DOPA uptake repertoire in the Mesocorticolimbic System, structural measurements and DNA Methylation. Methodology: Study Design: A prospective, pilot study. 30 un medicated Depressed patients and 30 Healthy volunteers will perform a \[18F\] FDOPA PET/MRI scans following a HAM-D questionnaire (Hamilton rating scale of depression) and blood tests. PET-MR (Biograph mMR, Siemens AG, Erlangen, Germany) scans will be performed using the tracer of dopamine precursor 3,4-dihydroxy-6-\[18F\]-fluoro-l-phenylalanine (\[18F\] FDOPA) that reflects L-dopa transport, L-aromatic amino acid decarboxylase activity, vesicular uptake and the number of dopamine nerve terminals. Measurements of dynamic F-DOPA parameters (Ki) and quantitative measurements of static F-DOPA ( SUVmax and SUVmean) will be performed in the ventral tagmental area (VTA), nucleus accombens (NAc) and pre-frontal cortex (PFC)which comprise the Mesocorticolimbic System, bilaterally. MRI sequences of T1, T2 3D measurements (assessing Volume) of the hippocampus, Hypothalamic-Pituitary gland and Mesocorticolimbic system, DTI measurements in the mesocorticolimbic dopaminergic tract and BOLD (resting-state f-MRI) in those brain networks. whole genome DNA Methylation from whole blood will be performed. To date there is no quantative standard of care evaluation tool that serves psychiatrists when assigning medication for newly diagnosed depressed patients. The manner in which medications are assigned are threw symptom evaluation and trial and error. Only a third of the patients achieve remission after the first line of treatment. SSRI's are most common type of medication used to treat Major Depression today. One third of patients remains un responsive even after the fourth line of treatment (of different types of medications). Anti depression medications way of action requires time to reach its effect and in many patients with no avail or even causing symptom's severity. The PET-MR multimodality imaging tool offers a cutting edge technology ideally fitted to measure brain disorders. The use of F-DOPA radio-ligand with the PET-MR constitutes a novelty in the imaging of the depressed brain. Dopamine is one of three of the monoamine neurotransmitters targeted by anti-depressive medication, sharing metabolistic agents. dopamine has been proven to be connected to the processing of emotion, motivation, hedonism and reward threw its action in the Meso-cortico-limbic system. Epigenetics is a regulatory system that determines gene expression. It is heritable in the one hand and reacts to environmental changes on the other. It has been shown to be involved in psychiatric disorders. PET-MR scans will be performed. DNA samples will be extracted from subject's whole blood samples taken prior to scans. Then it will be analyzed for whole genome DNA methylation. Taken together this novelty imaging technique and epigenetic mapping of peripheral markers can be used to better understand and personalize anti-depressive treatment compatibility.

Conditions

Depression

Outcome Measures

Primary Outcomes (1)

• 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F] FDOPA) uptake rate constant (K(i)) that reflects L-dopa transport.

  at base line

Study Arms (2)

depressed

un medicated diagnosed with major depression and scheduled to start SSRI treatment.

Other: no intervantion

healthy

healthy volunteers.

Other: no intervantion

Interventions

no intervantion OTHER

no intervention is being performed, only observational evaluations.

depressed; healthy

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Sample size: This is a pilot study for which a sample size of 60 subjects (30 healthy individuals and 30 patients) is required. Participant recruitment: Eligible consecutive patients, satisfying the inclusion/exclusion criteria, will be identified and recruited by the psychiatric clinic. Eligible healthy volunteers will be recruited with assigned pamphlet approved by IRB.

You may not qualify if:

• women.
• With no history of psychiatric diagnosis.
• History of any neurodegenerative disease or active oncologic disease.
• With no history of psychiatric medication intake.
• Patients treated with levodopa or any other medication known to interfere with the DAT or catechol O-methyltransferase inhibitors, or with dopamine receptor blocking / or catecholamine re-uptake blocking properties.
• Contraindication to MR imaging.
• study group- 30 Newly diagnosed depressed patient from the clinic of Dr. Lurie an extension of Shalvata Mental health center .
• Adult male patients between the age of 30-50 years old.
• Patients willing to participate with all the study procedures and sign informed consent form.
• A clinical diagnosis of major depression.
• With no history of psychiatric medication intake.
• Scheduled to be treated with SSRI.
• women.
• Psychiatric patients diagnosed and treated with any psychiatric medication.
• History of any neurodegenerative disease or active oncologic disease.

Sponsors & Collaborators

• Assuta Medical Center: lead

Biospecimen

Retention: SAMPLES WITH DNA

whole blood.

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Central Study Contacts

david groshar, MD

CONTACT

+972-37644364; davidg@assuta.co.il

Noa Zifman, MSc

CONTACT

+972-523755213; noaz@assuta.co.il

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: david groshar

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: January 20, 2017
• Study Start: March 1, 2017
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: January 20, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share