Evaluation of the Efficacy of Serotoninergic Antidepressants in Bulimia Nervosa, According to Brain Serotonin Profile Determined by Positron Emission Tomography With [18F] MPPF.

Evaluation of the Efficacy of Serotoninergic Antidepressants in Bulimia Nervosa, According to Brain Serotonin Profile Determined by Positron Emission Tomography With [18F] MPPF - a Multicenter Study

Bulimia nervosa (BN) is a serious mental illness characterized by massive food crises followed by anxiety and compensatory behaviours (vomiting more often). Recent data show an increasing prevalence and a serious prognosis, due to excess mortality by suicide but also somatic complications.

Two types of treatments are validated : serotoninergic antidepressants (SSRI) and psychotherapy. Many clinical trials confirm the effectiveness of the SSRI. But many studies also emphasize the important proportion of non-responders to SSRI, few of them analyze the reasons for this non-answer.

To better understand the mode of action of SSRI, we should analyse the serotonergic activity in the central nervous system in bulimia. Recently, specific brain 5HT1A serotonin receptor ligands ([18F] MPPF or [11 C] WAY-100635), were used in positron emission tomography (PET) to characterize the serotonergic abnormalities of bulimic patients. The ligand [18F] MPPF has the feature to be sensitive to the level of endogenous serotonin.

A first pilot study using PET with [18F] MPPF realized between the University Hospital of Saint Etienne and Lyon CERMEP showed a diffuse increase of the binding potential of [18F] MPPF in bulimic patients, suggesting a decrease in serotonin activity.

The brain regions affected were angular gyrus, medial frontal cortex, left insula, cingulate gyrus and orbitofrontal gyrus. These areas are involved in major bulimic symptoms (impulse, taste, instinct, anxiety and satiety). However, we noticed an interindividual heterogeneity of cortical binding of [18F] MPPF.

In front of the heterogeneity in terms of efficacity of SSRI and brain serotoninergic activity, it seems necessary to continues investigations, to determine if there is a link between brain serotonin profile and responding to SSRI in bulimia nervosa.

Study Overview

• Status: Completed
• Conditions: Bulimia Nervosa
• Intervention / Treatment: Drug: Antidepressants; Drug: Positron Emission Tomography (PET)

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Bron, France, 69678
    • Groupement Hospitalier Est - HCL
  • Clermont-Ferrand, France
    • CHU de Clermont-Ferrand
  • Grenoble, France, 38043
    • CHU Grenoble
  • Saint-Etienne, France, 42055
    • CHU Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient affiliated or entitled to a social security scheme
• Bulimic patients according to DSM-IV TR: minimum 2 bulimic crises (compulsive eating followed by compensatory behavior) / week for 3 weeks
• Patients who signed informed consent to the study
• BMI greater than or equal to 18.5 kg / m²

Exclusion Criteria:

• Against-indication to the SSRI or fluoxetine
• SSRI consumption in the previous three months
• Other addiction (except tobacco, for reasons of feasibility)
• Diagnosis of binge eating disorder or EDNOS (DSM-IV-TR)
• Patients with heart failure
• Against-indication for PET and / or MRI: pacemaker, intracerebral clips, prosthesis made of ferromagnetic material or claustrophobia
• Subjects with suspected pregnancy or in the second half of their menstrual cycle in the absence of oral contraceptives; positive Β-HCG test before the exam

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: boulimic; Analyse of serotoninergic brain activity (determined by positron emission tomography using [18F]MPPF) from bulimic patients treated with serotoninergic antidepressants during 3 months. The serotoninergic brain activity is measured before adnd after the serotoninergic antidepressant treatment.	Drug: Antidepressants; bulimic patients are treated during 3 months; Other Names: Fluoxetine; Drug: Positron Emission Tomography (PET); PET scan using [18F]MPPF is performed before and after (3 months)antidepressant treatment; Other Names: PET scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between [18F]MPPF Binding Potential (BP) and efficacy of antidepressant treatment	Correlation between efficacy of antidepressant treatment quantified by change from the baseline in number of bulimic crises and the change from the baseline in [18F]MPPF BP at 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between [18F]MPPF Binding Potential (BP) and psychometric scores	Correlation between change from the baseline in [18F]MPPF BP and change from the baseline in psychometric scores at 3 months	3 months
Correlation between [18F]MPPF Binding Potential (BP) and initial severity	Correlation between [18F]MPPF Binding Potential (BP) at 3 months and initial (month 0) disease severity quantified by numbers bulimic crises over last 2 weeks before the initial evaluation and psychometric scores at initial evaluation (day 0)	3 months
Change from baseline in [18F]MPPF Binding Potential (BP)	Comparison between [18F]MPPF Binding Potential (BP) before antidepressant treatment (day 0) and after antidepressant treatment (month 3)	3 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Bogdan GALUSCA, MD, CHU SAINT-ETIENNNE

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 9, 2015
• Primary Completion (ACTUAL): November 12, 2021
• Study Completion (ACTUAL): March 11, 2022

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 5, 2015
• First Posted (ESTIMATE): February 10, 2015

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: fluoxetine; bulimia; serotoninergic brain activity; serotoninergic antidepressant; brain serotonin profile; positon emission tomography
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Hyperphagia; Bulimia; Bulimia Nervosa; 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; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine; Antidepressive Agents
• Other Study ID Numbers: 1408170; 2015-000365-31 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No