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Completed

NCT Number: NCT02551029

fMRI and Visceral Perception Upon Capsaicin Infusion

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.

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Key information

Age range

18 year–65 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University Medical Center

Maastricht, 6229 ER, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Capsaicin

Other

Other names: Capsaicin oleoresina solution infusion into the duodenum.

Placebo

Other

Other names: Saline infusion into the duodenum

Primary outcomes

  1. Activation of the Nucleus of the Solitary Tract

    Time frame: During 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 outcomes

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

    Time frame: During 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

  2. Questionnaire for pain (Visual Analogue Scores)

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

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

  3. Questionnaire for depression and anxiety

    Time frame: During 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.

  4. Questionnaire for depression

    Time frame: During 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.

  5. Questionnaire for personality trait

    Time frame: During 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.

  6. Questionnaire for quality of life

    Time frame: During 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.

  7. Questionnaire for current affect scores

    Time frame: During 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.

  8. Questionnaire for current pain

    Time frame: During 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.

  9. Questionnaire for anxiety

    Time frame: During 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.

  10. Questionnaire for the assessment of Gastrointestinal symptom scores

    Time frame: During the test day (= day 1), before scanning

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

  11. Questionnaire for the assessment of Gastrointestinal symptom scores

    Time frame: During the test day (= day 1), before scanning

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

  12. Questionnaire for the assessment of early life traumata

    Time frame: During 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).

  13. Questionnaire for the assessment of gastrointestinal specific anxiety

    Time frame: During 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.

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Collaborators

  • KU Leuven

Registry information

Official study title

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

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
Sep 16, 2015
Registry last updated
Jun 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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