Olfactory and Brain Stimulations in Treatment-resistant Depression

NCT05661383 | Recruiting DMC

• 1 other identifier: 2022-A01967-36
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, double-blind, parallel-group controlled trial. The aim of this research project is to compare the clinical benefits achieved in patients with major depressive disorder (MDD) following two types of intervention: iTBS active alone or iTBS active combined with olfactory stimulations.

Conditions

Treatment-resistant Depression

Keywords

Depression; brain stimulation; anhedonia; odor

Outcome Measures

Primary Outcomes (1)

• Change in MADRS score before and after intervention to characterized the number of depressed patients who reach remission criteria (MADRS ≤ 10) in each group

  MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to intervention. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. Remission is defined as a Montgomery and Asberg Depression Rating Scale (MADRS) score less than or equal to 10 at the end of 50 sessions of iTBS

  4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.

Secondary Outcomes (8)

• Group differences in Montgomery-Asberg Depression Rating Scale (MADRS) score changes

  4 times : Before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.

• Group differences in Beck Depressive Inventory (BDI) score changes

  4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.

• Group differences in European Test of Olfactory Capabilities (ETOC) score changes

  2 times : Before the Intervention (J0), immediately following the end of the Intervention (J15)

• Group differences in the Chapman Social Anhedonia Scale (SAS)

  4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.

• the Chapman Physical Anhedonia Scale (PAS) score changes

  4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.

Study Arms (2)

iTBS active combined with an olfactory stimulation

EXPERIMENTAL

Non-invasive brain stimulation protocol (intermittent theta burst protocol (iTBS)) combined with pleasant odors delivered during the iTBS procol.

Device: Non-invasive brain stimulation protocol (intermittent theta burst protocol (iTBS)) combined with pleasant odors delivered during the iTBS procol.

iTBS active alone

ACTIVE COMPARATOR

Non-invasive brain stimulation protocol (intermittent theta burst protocol (iTBS)) delivered alone.

Device: Non-invasive brain stimulation protocol (intermittent theta burst protocol (iTBS)) delivered alone.

Interventions

Non-invasive brain stimulation protocol (intermittent theta burst protocol (iTBS)) combined with pleasant odors delivered during the iTBS procol. DEVICE

Device: MagPro X100 (MagVenture, Mag2Health, France) iTBS protocol targeting the left dorsolateral prefrontal cortex: 50 consecutive sessions allocated on 10 days (i.e., 5 sessions per working day, 1 hour apart, for 2 weeks). One iTBS session: burst of 3 pulses at 50 Hz repeated at 200 ms intervals for 2 s (i.e., at 5 Hz) at an intensity of 90% of rMT. A 2 s train of iTBS will be repeated every 10 s for a total of 1800 pulses per session. Pleasant odorants will be delivered using passive diffusers placed in the room dedicated to the iTBS protocol, during the all-treatment duration. During the inclusion phase, 10 odors known to be pleasant will be presented to the subject. The 3 best rated by the subject will be chosen for olfactory stimulations. During the iTBS session, a randomly selected odor from the 3 will be presented at the same time as the iTBS treatment.

iTBS active combined with an olfactory stimulation

Non-invasive brain stimulation protocol (intermittent theta burst protocol (iTBS)) delivered alone. DEVICE

Device: MagPro X100 (MagVenture, Mag2Health, France) iTBS protocol targeting the left dorsolateral prefrontal cortex: 50 consecutive sessions allocated on 10 days (i.e., 5 sessions per working day, 1 hour apart, for 2 weeks). One iTBS session: burst of 3 pulses at 50 Hz repeated at 200 ms intervals for 2 s (i.e., at 5 Hz) at an intensity of 90% of rMT. A 2 s train of iTBS will be repeated every 10 s for a total of 1800 pulses per session.

iTBS active alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• had a primary diagnosis of single-episode or recurrent non-psychotic major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria;
• scored 20 or over on the MADRS (Montgomery-Åsberg Depression Rating Scale) (Montgomery and Åsberg, 1979) and scored higher than 2 on the MADRS item 8 anhedonia factor score;
• sign a consent form before intervention.

You may not qualify if:

• a pre-existing condition that affects olfaction including congenital anosmia, upper respiratory tract infection, nasal and/or sinus disease, brain injury or nasal surgery; a neurological disease;
• other comorbid psychiatric disorders or substance abuse (except tobacco);
• contraindications to TMS (medical devices implanted or metallic foreign body in the head);
• pregnant or lactating mothers (controlled by urine pregnancy tests);
• measure of protection or guardianship of justice.

Sponsors & Collaborators

• Hôpital le Vinatier: lead
• Fondation de France: collaborator

Study Sites (1)

CH Le Vinatier

Bron, 69678, France

RECRUITING

Related Publications (1)

• Imbert L, Neige C, Dumas M, Bensafi M, Mandairon N, Brunelin J. Combining pleasant Olfactory and BRAin stimulations in treatment-resistant depression (COBRA): study protocol for a randomized controlled trial. Front Psychol. 2024 Dec 17;15:1451096. doi: 10.3389/fpsyg.2024.1451096. eCollection 2024.

  PMID: 39744036 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression; Anhedonia

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• BRUNELIN JEROME, PhD

  hospital le vinatier

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SARTELET Lydie

CONTACT

0437915531; lydie.sartelet@ch-le-vinatier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be block randomized (1:1) to receive either iTBS active combined with an olfactory stimulation or TBS active alone. Computer generated random numbers will be used to generate the allocation sequence. The allocation sequence will be handled by an independent person from the Administrative Department of the Hospital and will be unavailable to those who enroll and assign patients. Patients will be blind to their treatment assignment. Moreover, the medical doctors who will administer the clinical scales and the researchers that will analyze the data will be blinded to the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, single-center, randomized, double-blind, parallel-group controlled trial with two arms

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: December 22, 2022
• Study Start: January 27, 2024
• Primary Completion (Estimated): January 27, 2027
• Study Completion (Estimated): October 2, 2027
• Last Updated: July 24, 2025

Record last verified: 2025-07

Locations

FR (1)