Psycho-biological Substrates of Therapeutic Benefit of Thermal Cure on Generalized Anxiety Disorders (Insula-TOP)

Psycho-biological Substrates of Therapeutic Benefit of Thermal Cure on Generalized Anxiety Disorders (Insula-TOP)

Multicenter study comparing paroxetine (n=30) versus thermal cure (n=30) in patients with a diagnosis of Generalised Anxiety Disorders

Study Overview

• Status: Completed
• Conditions: Generalized Anxious Disorders
• Intervention / Treatment: Drug: Paroxetine; Other: Thermal cure

Detailed Description

Multicenter study comparing paroxetine (n=30) versus thermal cure (n=30) in patients with a diagnosis of Generalised Anxiety Disorders

Main objective is to quantify the therapeutic benefit of a thermal cure on generalized anxiety disorders and to understand the psycho-biological substrates of this improvement.

Secondary objectives:

• A decrease of Insula activity at rest during the answers to aversive pictures and during the task of subjective measurement of heartbeat.
• A decrease of sensibility to emotional interference by subliminal presentation of emotional words thanks to a lexical task and a color recognition task associated to simultaneous measurement of physiological indicator of emotional activity ( dermal resistance)

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Poitiers, France
    • Centre Hospitalier Henri Laborit
  • Saujon, France, 17600
    • Les thermes de Saujon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnostic of generalized anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV)
• No treatment by antidepressant for at least 2 months
• No treatment by anxiolytic/neuroleptic/bete blockers/antipsychotic for at least 3 weeks
• Global score of Hamilton Anxiety Scale (HAM-A) is greater or equal to 20
• Score of HAM-A symptoms greater or equal to 8
• Score of Hamilton Depressive Scale (HAM-D) lower or equal to 7
• Age: Participants will be males and females, 18-75 years of age included.
• For women, no ongoing pregnancy/ negative pregnancy test
• No wounds
• Affiliation to a social security system (recipient or assignee)
• Signed written inform consent form

Exclusion Criteria:

• Treatment by antidepressant for at least 2 months or a treatment by anxiolytic, neuroleptic for at least 3 weeks
• Psychotropic treatment (antidepressant, anxiolytic and neuroleptic) between the preinclusion and inclusion
• Psychotherapy during the 3 months prior to the inclusion
• Thermal cure during the 6 months prior to the inclusion
• Treatment by paroxetine for at least 1 month with dose equal or superior to 20 mg per day during the 12 months prior to the inclusion
• Contraindication to paroxetine
• Enhanced protection (minors, pregnancies women, nursing women,people deprived of liberty by administrative or judicial decision, ...)
• Blood donation during the 3 months prior to the inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paroxetine; Paroxetine (Deroxat®) Posology : 20 mg per day for 3 weeks. After 2 weeks of treatments, if indicated, physicians will prescribe until 50 mg.	Drug: Paroxetine; Deroxat® (20 mg/day) 3 week; can be increase on week 2 until 50 mg.
Other: Thermal cure; This study is controlled with a comparator which is the Thermal cure. Thermal cure is realized for 3 weeks.	Other: Thermal cure; Thermal cure is realized for 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decrease Insula activity during a resting state task	The evaluation of primary end point is performed between day 1 and day 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes of HAM-A score between day 1 and day 24.	The evaluation of primary end point is performed between day 1 and day 24
Sensibility non conscientious to emotional interference in lexical task and in color identification task	D= Day D1/D24/D56
Modulation of electrodermal response during presentation of predictive stimuli on aversive images and its links to the subjective view of emotional state	D= Day D24
Modulation of electrodermal response during presentation of predictive stimuli on aversive images and insula activation	D= Day D24
Lost of significant correlation (Day 24) between HAM-A score, introspective acuity and insula hyperactivation	D= Day D24
Evolution (Day 1 and Day 24) of the correlation between HAM-A global score and 1- the measure of heartbeat 2- emotional reactivity during aversive images task.	D= Day D1/D24.
Difference (Day 1 and Day 24) of correlations between the symptoms severity and the activation of insula cortex during 1-aversive images task, 2-heartbeat measure task.	D= Day D1/D24.
Evaluation of efficacy of the thermal cure Day 56 using HAM-A score	D= Day D56

Collaborators and Investigators

• Sponsor: Centre Hospitalier Henri Laborit
• Collaborators: Poitiers University Hospital; Association Francaise pour la Recherche Thermale; Les thermes de Saujon; Centre National de la Recherche Scientifique (CeRCA, umr 7295), France
• Investigators: Principal Investigator: JAAFARI Nematollah, MD-PhD, Centre Hospitalier Henri Laborit; Study Chair: INGRAND Pierre, MD-PhD-PU-PH, Centre d'investigation clinique INSERM CIC P802

Publications and helpful links

General Publications

• Jaafari N, Rachid F, Rotge JY, Polosan M, El-Hage W, Belin D, Vibert N, Pelissolo A. Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: a review. World J Biol Psychiatry. 2012 Mar;13(3):164-77. doi: 10.3109/15622975.2011.575177. Epub 2011 May 30.
• Jaafari N, Baup N, Bourdel MC, Olie JP, Rotge JY, Wassouf I, Sharov I, Millet B, Krebs MO. Neurological soft signs in OCD patients with early age at onset, versus patients with schizophrenia and healthy subjects. J Neuropsychiatry Clin Neurosci. 2011 Fall;23(4):409-16. doi: 10.1176/jnp.23.4.jnp409.
• Jaafari N, Aouizerate B, Tignol J, El-Hage W, Wassouf I, Guehl D, Bioulac B, Daniel ML, Lacoste J, Gil R, Burbaud P, Rotge JY; Insight Study Group. The relationship between insight and uncertainty in obsessive-compulsive disorder. Psychopathology. 2011;44(4):272-6. doi: 10.1159/000323607. Epub 2011 May 6. Erratum In: Psychopathology. 2011;44(5):319.
• Girard SL, Gauthier J, Noreau A, Xiong L, Zhou S, Jouan L, Dionne-Laporte A, Spiegelman D, Henrion E, Diallo O, Thibodeau P, Bachand I, Bao JY, Tong AH, Lin CH, Millet B, Jaafari N, Joober R, Dion PA, Lok S, Krebs MO, Rouleau GA. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet. 2011 Jul 10;43(9):860-3. doi: 10.1038/ng.886.
• Dubois O, Salamon R, Germain C, Poirier MF, Vaugeois C, Banwarth B, Mouaffak F, Galinowski A, Olie JP. Balneotherapy versus paroxetine in the treatment of generalized anxiety disorder. Complement Ther Med. 2010 Feb;18(1):1-7. doi: 10.1016/j.ctim.2009.11.003. Epub 2010 Jan 6.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2017
• Primary Completion (Actual): January 8, 2020
• Study Completion (Actual): February 5, 2020

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 11, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: paroxetine; Generalized anxious disorders; Thermal cure
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Anxiety Disorders; 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; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine
• Other Study ID Numbers: InsulaTOP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No