fMRI and Visceral Perception Upon Capsaicin Infusion

Maastricht University Medical Center19 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Irritable Bowel Syndrome Colonic Diseases, Functional Dyspepsia Gastrointestinal Diseases

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Activation of the Nucleus of the Solitary Tract

the BOLD (Voxel-wise blood oxygenation level dependent) signal activity in the Nucleus of the Solitary Tract during capsaicin infusion compared to placebo

Time frame: During duodenal capsaicin and placebo infusion between t=0 and and t=38 minutes

Secondary Outcomes

Activity and connectivity in the Cingulate Cortex, Insula, Thalamus, Prefrontal Cortex, Primary and Secondary Somatosensory Cortex, Amygdala, PAG

the functional BOLD signal activity in the above-mentioned brain structures during capsaicin infusion compared to placebo

Time frame: During duodenal capsaicin and placebo infusion between t=0 and and t=60 minutes

Questionnaire for pain (Visual Analogue Scores)

Scores range from 0 \[no pain\] to 10 \[worst possible pain\].

Time frame: During capsaicin and placebo infusion between t=0 and and t=38 minutes

Questionnaire for depression and anxiety

Hospital Anxiety and Depression Scale (HADS). Has 14 items (7 for depression, 7 for anxiety) with a 4 points likert scale (0-3). Scores for depression and anxiety range from 0-21 and studies identified 8 as the cutoff-point.

Time frame: During the test day, before scanning

Questionnaire for depression

PHQ-9 scores (patient health questionnaire). The questionnaire has 9 items with a 4 points likert scale (0-3) and a total score of 27. A total score of 0-4 indicates none to minimal depressive symptoms, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe.