fMRI and Visceral Perception Upon Capsaicin Infusion

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Capsaicin

Placebo

About this trial

This is an interventional basic science trial for Irritable Bowel Syndrome focused on measuring Magnetic Resonance Imaging, Brainstem, Solitary Nucleus, Visceral Nervous System, Transient Receptor Potential Channels

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

Maastricht University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Duodenal capsaicin infusion

Placebo (saline)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Questionnaire for pain (Visual Analogue Scores)

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

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.

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.

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.

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.

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.

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.

Questionnaire for anxiety

GAD-7 scores, for screening and severity measuring of generalized anxiety disorder (GAD). GAD-7 has seven items, 0-3 scale.

Questionnaire for the assessment of Gastrointestinal symptom scores

Scores of the GSRS, scale 1-7, generates subscores for abdominal pain, reflux, diarrhea, constipation, indigestion

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.

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).

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.

Full Information

NCT ID

NCT02551029

First Posted

August 25, 2015

Last Updated

June 5, 2020

Sponsor

Maastricht University Medical Center

Collaborators

KU Leuven

1. Study Identification

Unique Protocol Identification Number

NCT02551029

Brief Title

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

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

February 2016 (Actual)

Primary Completion Date

July 26, 2019 (Actual)

Study Completion Date

July 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Maastricht University Medical Center

Collaborators

KU Leuven

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Randomized

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Duodenal capsaicin infusion

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo (saline)

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Other

Intervention Name(s)

Capsaicin

Other Intervention Name(s)

Capsaicin oleoresina solution infusion into the duodenum.

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

Saline infusion into the duodenum

Primary Outcome Measure Information:

Title

Activation of the Nucleus of the Solitary Tract

Description

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 Outcome Measure Information:

Title

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

Description

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

Title

Questionnaire for pain (Visual Analogue Scores)

Description

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

Title

Questionnaire for depression and anxiety

Description

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

Title

Questionnaire for depression

Description

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.

Time Frame