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fMRI and Visceral Perception Upon Capsaicin Infusion

Not Applicable
Completed
Conditions
Visceral Pain
Irritable Bowel Syndrome
Colonic Diseases, Functional
Gastrointestinal Diseases
Abdominal Pain
Dyspepsia
Interventions
Other: Placebo
Other: Capsaicin
Registration Number
NCT02551029
Lead Sponsor
Maastricht University Medical Center
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
19
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Placebo (saline)PlaceboThrough a naso-duodenal tube, a saline solution will be infused into the duodenum.
Duodenal capsaicin infusionCapsaicinThrough a naso-duodenal tube, a capsaicin solution will be infused into the duodenum.
Primary Outcome Measures
NameTimeMethod
Activation of the Nucleus of the Solitary TractDuring duodenal capsaicin and placebo infusion between t=0 and and t=38 minutes

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
NameTimeMethod
Activity and connectivity in the Cingulate Cortex, Insula, Thalamus, Prefrontal Cortex, Primary and Secondary Somatosensory Cortex, Amygdala, PAGDuring duodenal capsaicin and placebo infusion between t=0 and and t=60 minutes

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

Questionnaire for pain (Visual Analogue Scores)During capsaicin and placebo infusion between t=0 and and t=38 minutes

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

Questionnaire for depression and anxietyDuring the test day, before scanning

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

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

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

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

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

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

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

Scores of the GSRS-IBS, scale 1-7, generates subscores for abdominal pain, bloating, constipation, diarrhea, satiety.

Questionnaire for the assessment of early life traumataDuring the test day (= day 1), before scanning

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

Scores of the Visceral Sensitivity Index, a 15 item questionnaire, scale 1-6, assesses gastrointestinal (GI)-specific anxiety.

Trial Locations

Locations (1)

Maastricht University Medical Center

🇳🇱

Maastricht, Netherlands

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