fMRI and Visceral Perception Upon Capsaicin Infusion

Irritable Bowel Syndrome Clinical Trial

Official title:

Brain and Brainstem Activation Following Duodenal Nociceptive Stimulation With Capsaicin, an Exploratory High-resolution fMRI Study in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02551029
• Other study ID #: METC 152048
• Secondary ID: NL51770.068.15ME
• Status: Completed
• Phase: N/A
• Start date: February 2016
• Est. completion date: July 26, 2019

Study information

• Verified date: June 2020
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 26, 2019
• Est. primary completion date: July 26, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Abdominal Pain
• Colonic Diseases
• Colonic Diseases, Functional
• Digestive System Diseases
• Dyspepsia
• Gastrointestinal Diseases
• Irritable Bowel Syndrome
• Visceral Pain

Intervention

Other:
• Capsaicin

• Placebo

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	KU Leuven

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	During duodenal capsaicin and placebo infusion between t=0 and and t=38 minutes
Secondary	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	During duodenal capsaicin and placebo infusion between t=0 and and t=60 minutes
Secondary	Questionnaire for pain (Visual Analogue Scores)	Scores range from 0 [no pain] to 10 [worst possible pain].	During capsaicin and placebo infusion between t=0 and and t=38 minutes
Secondary	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.	During the test day, before scanning
Secondary	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.	During the test day (= day 1), before scanning
Secondary	Questionnaire for personality trait	BIG FIVE Inventory, the Big Five Inventory (BFI) survey that measures the big five dimensions of personality (extraversion, neuroticism, consciousness, agreeableness, and openness to experience). The questionnaire has 44 items.	During the test day (= day 1), before scanning
Secondary	Questionnaire for quality of life	SF-36 (quality of life) scores, The Short Form (36) Health Survey questionnaire of 36 items, scale 1-6, generates a physical and a mental QoL component summary.	During the test day (= day 1), before scanning
Secondary	Questionnaire for current affect scores	PANAS-SF (current affect) scores, Positive and Negative Affect Schedule. This is a 20 item questionnaire (scale 1-5) total scores can range from 10 - 50, with higher scores representing higher levels of positive affect.	During the test day (= day 1), before scanning
Secondary	Questionnaire for current pain	Brief Pain Inventory (BPI) scores, The BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score is calculated from the four items about pain intensity. Each item is rated from 0, no pain, to 10, pain as bad as you can imagine, and contributes with the same weight to the final score, ranging from 0 to 40. The pain interference score corresponds to the item on pain interference. The seven sub- items are rated from 0, does not interfere, to 10, completely interferes, and contributes with the same weight to the final score, ranging from 0 to 70.	During the test day (= day 1), before scanning
Secondary	Questionnaire for anxiety	GAD-7 scores, for screening and severity measuring of generalized anxiety disorder (GAD). GAD-7 has seven items, 0-3 scale.	During the test day (= day 1), before scanning
Secondary	Questionnaire for the assessment of Gastrointestinal symptom scores	Scores of the GSRS, scale 1-7, generates subscores for abdominal pain, reflux, diarrhea, constipation, indigestion	During the test day (= day 1), before scanning
Secondary	Questionnaire for the assessment of Gastrointestinal symptom scores	Scores of the GSRS-IBS, scale 1-7, generates subscores for abdominal pain, bloating, constipation, diarrhea, satiety.	During the test day (= day 1), before scanning
Secondary	Questionnaire for the assessment of early life traumata	Scores of the ETISR-SF, The Early Trauma Inventory Self Report - Short Form comprises of 27 items, divided into four dimensions (general trauma, physical abuse, emotional abuse and sexual abuse) and scored on a dichotomous scale (Yes/No).	During the test day (= day 1), before scanning
Secondary	Questionnaire for the assessment of gastrointestinal specific anxiety	Scores of the Visceral Sensitivity Index, a 15 item questionnaire, scale 1-6, assesses gastrointestinal (GI)-specific anxiety.	During the test day (= day 1), before scanning