fMRI and Visceral Perception Upon Capsaicin Infusion

NCT02551029 | Completed

• 2 other identifiers: METC 152048NL51770.068.15
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

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

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

• Questionnaire for pain (Visual Analogue Scores)

  During capsaicin and placebo infusion between t=0 and and t=38 minutes

• Questionnaire for depression and anxiety

  During the test day, before scanning

• Questionnaire for depression

  During the test day (= day 1), before scanning

• Questionnaire for personality trait

  During the test day (= day 1), before scanning

Study Arms (2)

Duodenal capsaicin infusion

EXPERIMENTAL

Through a naso-duodenal tube, a capsaicin solution will be infused into the duodenum.

Other: Capsaicin

Placebo (saline)

PLACEBO COMPARATOR

Through a naso-duodenal tube, a saline solution will be infused into the duodenum.

Other: Placebo

Interventions

Capsaicin OTHER

Also known as: Capsaicin oleoresina solution infusion into the duodenum.

Duodenal capsaicin infusion

Placebo OTHER

Also known as: Saline infusion into the duodenum

Placebo (saline)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• KU Leuven: collaborator

Study Sites (1)

Maastricht University Medical Center

Maastricht, 6229 ER, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 34799534 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome; Colonic Diseases, Functional; Dyspepsia; Gastrointestinal Diseases; Abdominal Pain; Visceral Pain

Interventions

Capsaicin

Condition Hierarchy (Ancestors)

Colonic Diseases; Intestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Nociceptive Pain

Intervention Hierarchy (Ancestors)

Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Officials

• A.A.M. Masclee, Prof. MD. PhD

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 16, 2015
• Study Start: February 1, 2016
• Primary Completion: July 26, 2019
• Study Completion: July 26, 2019
• Last Updated: June 9, 2020

Record last verified: 2020-06

Locations

NL (1)