TMS in Inflammatory Bowel Disease

NCT ID: NCT04956159

Last Updated: 2023-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-01

Study Completion Date

2022-10-07

Brief Summary

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Transcranial magnetic stimulation (rTMS) has demonstrated diagnostic and therapeutic potential for a number of conditions and is an approved treatment for depression. Inflammatory Bowel Disease (IBD) has a significant impact on mental health, and comorbid maladaptive behaviors and pain are highly prevalent in patients with IBD and are often under-treated.

The investigators predict TMS will improve comorbid maladaptive behavior (heightened interoceptive awareness, sleep, fatigue, catastrophizing, anxiety and depression), reduce pain and improve quality of life in persons with inflammatory bowel disease (IBD). Further, TMS benefits will be associated with changes in gut microbiome as measured by stool, blood and urine samples and normalization of IBD-associated changes in brain structure and/or function as measured by magnetic resonance imaging (MRI).

Detailed Description

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Background and rationale:

Comorbid maladaptive behaviors and pain are highly prevalent in patients with IBD and are often under-treated. These comorbidities lack effective therapies and thus complicate medical management, adversely impact patient outcome and health, and increase the resource burden on the healthcare system. Development of effective treatment delivery is therefore vital. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive form of brain stimulation in which an electric pulse generator placed at the scalp produces a rapidly changing magnetic field at biologically relevant frequencies to induce a stimulating electrical current at targeted sites in the brain. rTMS has demonstrated diagnostic and therapeutic potential for a number of conditions, including Alzheimer's disease, autism, bipolar disorder, epilepsy, chronic pain, major depressive disorder, Parkinson's disease, post-traumatic stress disorder (PTSD), schizophrenia (negative symptoms), obsessive-compulsive disorder (OCD), and for the cessation of smoking. To date, however, rTMS has not been used to treat the mental health issues and symptoms observed in persons with IBD. The investigators will develop rTMS interventions for IBD to target comorbid maladaptive behaviors and pain using evidence-based knowledge of TMS effectiveness for other chronic medical conditions.

Research Question:

Compared to sham, does twice daily intermittent theta-burst stimulation rTMS delivered to the left dorsolateral prefrontal cortex for two weeks (20 sessions) improve comorbid maladaptive behavior (heightened interoceptive awareness, sleep, fatigue, catastrophizing, anxiety and depression), reduce pain and improve quality of life in persons with inflammatory bowel disease (IBD)? Further, will TMS benefits be associated with changes in gut microbiome and normalization of IBD-associated changes in brain structure and/or function as measured by magnetic resonance imaging (MRI)?

Methods:

Forty male and female IBD (Chron's Disease (CD) and Ulcerative Colitis (UC)) patients with co-morbid anxiety and depression will be recruited for this study.

Patients will be randomized 1:1 to TMS or sham TMS according to a computer-generated randomization list from eligible patients identified from the cohort study. Randomization will be stratified by type of IBD (UC versus CD). Patients will be randomized 1:1 to 2 weeks of twice-daily active or sham TMS. The investigators will utilize intermittent theta-burst stimulation (iTBS 600 pulses per session delivered as triplets at 50Hz repeated at 5Hz at 80% resting motor threshold) delivered to the left dorsolateral prefrontal cortex (DLPFC) using a MagPro X100 stimulator and a COOL-B70 (active) or MCF-P-B70 (placebo) coil. Participants will receive 20 treatments over two weeks. All participants allocated to the double-blind phase will be offered 2 weeks of open-label twice-daily iTBS to the left DLPFC if they do not achieve 50% reduction in QIDS-SR score during the double-blind phase.

Baseline characterization will include demographic information, self-reported measures of comorbid maladaptive behaviors and pain, neurocognitive tests, analysis of IBD symptoms, microbiome analysis

Participants will undergo an MRI of the brain prior to receiving treatment for localization of the DLPFC, as well as characterization of volumetric imaging, white matter imaging, resting state activity and inflammation imaging. A second MRI will be repeated characterizing these same parameters after the conclusion of the sham-controlled treatment (week 2).

Stool, blood and urine samples will be collected at baseline, after the conclusion of the sham-controlled treatment (week 2) and 4 weeks follow up (week 6). These will be used for assessment of fecal calprotectin, fecal bacterial and fungal microbiome, inflammatory markers and metabolomic analysis.

Brief, computerized neurocognitive tests will be administered at baseline, after TMS treatment (week 2) and 4 week follow up (week 6)

Conditions

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Inflammatory Bowel Diseases Maladaptive Behavior Associated With Physical Illness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Active iTBS rTMS

The active arm involves magnetic stimulation of the brain to the left dorsolateral prefrontal cortex (DLPFC) twice daily for two weeks (20 sessions). The active arm will be receiving intermittent Theta-Burst (iTBS) repetitive Transcranial Magnetic Stimulation (rTMS) to deliver magnetic pulses.

Group Type ACTIVE_COMPARATOR

iTBS repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type DEVICE

rTMS is a non-invasive procedure in which cerebral electrical activity is influenced by a rapidly changing magnetic field. The magnetic field is created by a plastic-encased coil which is placed over the patient's scalp. The magnetic field can be directed onto specific areas of the brain. rTMS can modulate cerebral activity by low or high frequencies. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region and help symptoms of depression and anxiety.

Sham iTBS rTMS

sham rTMS treatment involves scalp stimulation with no magnetic pulse twice daily for two weeks (20 sessions). Sham rTMS involves only the click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered to the brain.

Group Type SHAM_COMPARATOR

Sham rTMS

Intervention Type DEVICE

Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Interventions

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iTBS repetitive Transcranial Magnetic Stimulation (rTMS)

rTMS is a non-invasive procedure in which cerebral electrical activity is influenced by a rapidly changing magnetic field. The magnetic field is created by a plastic-encased coil which is placed over the patient's scalp. The magnetic field can be directed onto specific areas of the brain. rTMS can modulate cerebral activity by low or high frequencies. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region and help symptoms of depression and anxiety.

Intervention Type DEVICE

Sham rTMS

Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Intervention Type DEVICE

Other Intervention Names

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MAGPRO X100 stimulator MAGPRO X100 stimulator

Eligibility Criteria

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Inclusion Criteria

* confirmed diagnosis of IBD, demonstrated to be in endoscopic remission (Mayo Endoscopic Subscore \[for UC\] 0 or 1, or Simple Endoscopic Score for CD ≤4) or biomarker remission (fecal calprotectin \<250 ug/g) within 6 months of randomization
* ≥8 on the Hospital Anxiety and Depression Scale
* on stable IBD-related and psychotropic medications for the four weeks preceding randomization

Exclusion Criteria

* severely active IBD (Mayo score \> 9, HBI \> 16)
* require systemic corticosteroids
* initiated biologic treatment within the preceding three months
* suicidal ideation
* psychosis
* having failed ECT
* previous rTMS treatment (for blinding integrity)
* contraindications for MRI
* Use of benzodiazepines or GABA agonists
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IMAGINE (Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects)

UNKNOWN

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Calgary

Calgary, Alberta, Canada

Site Status

Countries

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Canada

Other Identifiers

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REB20-1272

Identifier Type: -

Identifier Source: org_study_id

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