Clinical trial NCT02551029: fMRI and Visceral Perception Upon Capsaicin Infusion
Official title: Brain and Brainstem Activation Following Duodenal Nociceptive Stimulation With Capsaicin, an Exploratory High-resolution fMRI Study in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Colonic Diseases, Functional
Dyspepsia
Gastrointestinal Diseases
Abdominal Pain
Visceral Pain
Keywords: Magnetic Resonance Imaging
Brainstem
Solitary Nucleus
Visceral Nervous System
Transient Receptor Potential Channels
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2015-09-16
Enrollment: 19
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Brain imaging has shown abnormal brain activations in response to visceral stimulation in patients with the Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD). To investigate the possible role of the Nucleus of the Solitary Tract (NTS), the primary relay station in the brainstem for vagal afferents, its activation in IBS and functional dyspepsia patients will be evaluated. Prior to this, an exploratory study in healthy volunteers will be conducted. This will be the first high magnetic field fMRI study (7T) evaluating the possible role of NTS activation in visceral abdominal pain. Moreover, this will be the first pharmacological fMRI study using duodenal capsaicin infusion as a chemical stimulus, which is more physiological than mechano-stimulation in the upper gastrointestinal tract.


Eligibility criteria: Inclusion Criteria:

* Of female sex
* Based on medical history and previous examination, no gastrointestinal complaints can be defined.
* Age between 18 and 65 years.
* BMI between 18 and 30 kg/m2
* Women in fertile age (\<55 years old) must use contraception or be postmenopausal for at least two years.
* All subjects should be right-handed.

Exclusion Criteria:

* Presence of metallic prostheses, pacemakers, metal clips on blood vessels, metal parts in the eye, an intrauterine device, metal braces, tattoos and/or other metal objects;
* History of major head trauma or head/brain surgery;
* History of claustrophobia;
* History of severe or chronic cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol;
* Use of medication, including vitamin and iron supplementation, except oral contraceptives, within 14 days prior to start of the study;
* Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgment of the principle investigator);
* Pregnancy, lactation, wish to become pregnant;
* High alcohol consumption (\>15 alcoholic consumptions per week);
* Using drugs of abuse;
* Self-admitted HIV-positive state;
* Known allergic reaction to capsaicin;
* High intake of spicy (capsaicin containing) food (meaning an estimated intake of \> than 1.5mg/day), due to possible desensitization of the capsaicin receptor TRPV1 (see further below);
* Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study;
* Any evidence of structural brain abnormalities examined by anatomical MRI will lead to exclusion.

Primary outcomes:
measure: Activation of the Nucleus of the Solitary Tract
timeFrame: During duodenal capsaicin and placebo infusion between t=0 and and t=38 minutes
Secondary outcomes:
measure: Activity and connectivity in the Cingulate Cortex, Insula, Thalamus, Prefrontal Cortex, Primary and Secondary Somatosensory Cortex, Amygdala, PAG
timeFrame: During duodenal capsaicin and placebo infusion between t=0 and and t=60 minutes
measure: Questionnaire for pain (Visual Analogue Scores)
timeFrame: During capsaicin and placebo infusion between t=0 and and t=38 minutes
measure: Questionnaire for depression and anxiety
timeFrame: During the test day, before scanning
measure: Questionnaire for depression
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for personality trait
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for quality of life
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for current affect scores
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for current pain
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for anxiety
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for the assessment of Gastrointestinal symptom scores
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for the assessment of Gastrointestinal symptom scores
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for the assessment of early life traumata
timeFrame: During the test day (= day 1), before scanning
measure: Questionnaire for the assessment of gastrointestinal specific anxiety
timeFrame: During the test day (= day 1), before scanning
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
Study officials:
affiliation: Maastricht University
name: A.A.M. Masclee, Prof. MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beckers AB, van Oudenhove L, Weerts ZZRM, Jacobs HIL, Priovoulos N, Poser BA, Ivanov D, Gholamrezaei A, Aziz Q, Elsenbruch S, Masclee AAM, Keszthelyi D. Evidence for engagement of the nucleus of the solitary tract in processing intestinal chemonociceptive input irrespective of conscious pain response in healthy humans. Pain. 2022 Aug 1;163(8):1520-1529. doi: 10.1097/j.pain.0000000000002538. Epub 2021 Nov 15.