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Opium Tincture Against Chronic Diarrhea - Healthy

Primary Purpose

Chronic Diarrhea

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Opium tincture
Placebo
Sponsored by
Asbjørn Mohr Drewes
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Chronic Diarrhea focused on measuring Diarrhea, Constipation, Gastrointestinal transit

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Signed informed consent before any study specific procedures Able to read and understand Danish Male or female with an age of 20 years or more The researcher believes that the participant understands what the study entails, are capable of following instructions, can attend when needed, and are expected to complete the study. The investigator will ensure that fertile female participants have a negative pregnancy test before each treatment visit and use contraception during the entity of the study. Opioid naïve (in this study "opioid naïve" is defined as a person who does not have a history of opioid use/addiction. If the opioids were used more than five years before the start of experiment as an analgesic to treat pain post-surgery etc., this person will be considered opioid naïve. If the person has never used opioids to treat pain but has participated in pain studies where opioids were given more than a year before this experiment, this person will be considered opioid naïve) Healthy (assessed by a study-affiliated medical doctor) Exclusion Criteria: Known allergy towards pharmaceutical compounds similar to Dropizol. Participation in other studies within 14 days of first visit (1 year if opioids involved). Expected need of medical/surgical treatment during the study History of psychiatric illness (e.g. mental retardation, schizophrenia, affective disorders (depression), personality disorders or treatment with psychoactive medications) History of substance abuse (e.g. alcohol, nicotine, tetrahydrocannabinol (THC), benzodiazepine, central stimulants and/or opioids) Family history of substance abuse Known increased intracranial pressure Known major stenosis of the intestines Planned MRI within the next 3 months Metal implants or pacemaker Known severe decreased renal function (defined as estimated glomerular filtration rate (eGFR) below 45) Known severe decreased hepatic function (defined as Child-Pugh class B or higher) Treatment with Monoamine oxidase (MAO) inhibitors during the entity of the study Known severe chronic obstructive pulmonary disease (COPD) or acute severe asthma (defined as forced expiratory volume in 1 second (FEV1) below 50 % or acute ongoing exacerbation) Known cor pulmonale Female participants that are lactating Medicine known to affect gastrointestinal motility must not be initiated during the entity of the study Use of any analgesic medication within 48 hours before start as well as for the duration of the study (urine drug test will be performed prior to treatment start). Intake of alcohol within 48 hours before start of study period as well as for the duration of the study.

Sites / Locations

  • Aalborg University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Opium tincture

Placebo

Arm Description

Administration of opium tincture (Dropizol)

Administration of placebo (identical to opium tincture in taste and appearance)

Outcomes

Primary Outcome Measures

Gastrointestinal transit
Difference in hours from ingestion of a 3D Transit Capsule to expulsion of the capsule during active and placebo treatment

Secondary Outcome Measures

Colonic motility patterns
Number of motility patterns in the colon measured by the 3D Transit Capsule
Bowel movement frequency
Number of spontaneous bowel movements per day
Stool consistency
Rated on the Bristol Stool Form Scale (ranging from type 1 (constipation) - type 7 (diarrhea))
Pupil diameter
Measured in mm
General cognition
Evaluated using the Mini-Mental State Examination
Reaction time
Measured in milliseconds (ms) from a sound was provided and until the participant pressed a button
Short-term memory
Measured as number of digits correctly remembered after visual presentation
Gastrointestinal symptoms
Measured on the Gastrointestinal Symptom Rating Score (GSRS) questionnaire (ranging from 0 (no discomfort) to 6 (very severe discomfort)
Constipation symptoms
Measured on the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire (ranging from 0 (symptom absent) to 4 (very severe).
Electroencephalography spectral analysis
40 electrodes will be used to record EEG during a period of 5 minutes rest. The results will be used to model connectivity between brain centres as well as the dominating centres of brain. EEG power will be assessed in the Delta, Theta, Alpha, Beta, and Gamma bands between 1 and 70 Hertz. Finally inverse modelling will be conducted to explore the dominating centres of brain activity.
Pain tolerance threshold
Pressure will be applied to the tibial bone and the quadriceps muscle by a handheld pressure algometer. The pain tolerance threshold (measured in kPa) is reached when the participant reports the pain to be intolerable
Conditioned pain modulation
The left hand of the participant is immersed in 2.0 degree (celsius) cold water for up to 2 minutes or until the pain becomes intolerable. The participant is asked to rate the pain on a 10-point Visual Analogue Scale (0 being no pain and 10 being worst imaginable pain) every 10 seconds during the test.
Gastric half emptying time
Analysis of gastric half emptying time after ingestion of a standardized meal measured by MRI
Gastric contraction assessment
Analysis of gastric contraction including amplitude and frequency of contractions after ingestion of a standardized meal measured by MRI
Small bowel motility assessment
Analysis of small bowel motility after ingestion of a standardized meal measured using dynamic MRI images. A semi-automated analysis software enables registration of small bowel motility with the calculation of regional motility maps and quantification of motility indices.
Small bowel water content
Analysis of small bowel water content measured using heavily T2-weighted MRI images
Colon volume
Volumetric quantification of the colon measured using T2-weighted MRI images
Estimated gastrointestinal transit time
Using DIXON images, location of three capsules filled with contrast fluid ingested 24 hours before MRI scan

Full Information

First Posted
January 6, 2023
Last Updated
January 27, 2023
Sponsor
Asbjørn Mohr Drewes
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1. Study Identification

Unique Protocol Identification Number
NCT05702190
Brief Title
Opium Tincture Against Chronic Diarrhea - Healthy
Official Title
Opium Tincture Against Chronic Diarrhea - Healthy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
March 9, 2021 (Actual)
Primary Completion Date
June 1, 2022 (Actual)
Study Completion Date
June 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Asbjørn Mohr Drewes

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to investigate the mechanistic anti-propulsive effects of opium tincture on the gastrointestinal tract of a cohort of healthy participants.
Detailed Description
Opium tincture is used a symptomatic drug against chronic diarrhea even though no clinical studies have investigated the effect on gastrointestinal function. With this randomized, double-blind, placebo-controlled cross-over trial in 20 healthy participants, the investigators wish to provide evidence-based insights into the effects of opium tincture on gastrointestinal function. Additionally, effects on the central nervous system will be investigated a tertiary aim.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Diarrhea
Keywords
Diarrhea, Constipation, Gastrointestinal transit

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Opium tincture
Arm Type
Active Comparator
Arm Description
Administration of opium tincture (Dropizol)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Administration of placebo (identical to opium tincture in taste and appearance)
Intervention Type
Drug
Intervention Name(s)
Opium tincture
Other Intervention Name(s)
Dropizol
Intervention Description
Self-administration of opium tincture (10 mg/ml) as 2x5 drops on day 1, 3x10 drops on days 2-8, and 1x10 drops on day 9 in each study period.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Self-administration of placebo as 2x5 drops on day 1, 3x10 drops on days 2-8, and 1x10 drops on day 9 in each study period.
Primary Outcome Measure Information:
Title
Gastrointestinal transit
Description
Difference in hours from ingestion of a 3D Transit Capsule to expulsion of the capsule during active and placebo treatment
Time Frame
Measurement started on day 2 of each study period until expulsion of the capsule (typically 24-48 hours after)
Secondary Outcome Measure Information:
Title
Colonic motility patterns
Description
Number of motility patterns in the colon measured by the 3D Transit Capsule
Time Frame
Measurement started on day 2 of each study period until expulsion of the capsule (typically 24-48 hours after)
Title
Bowel movement frequency
Description
Number of spontaneous bowel movements per day
Time Frame
From day 1 to day 9
Title
Stool consistency
Description
Rated on the Bristol Stool Form Scale (ranging from type 1 (constipation) - type 7 (diarrhea))
Time Frame
From day 1 to day 9
Title
Pupil diameter
Description
Measured in mm
Time Frame
Day 1, 6, and 9
Title
General cognition
Description
Evaluated using the Mini-Mental State Examination
Time Frame
Day 1, 6, and 9
Title
Reaction time
Description
Measured in milliseconds (ms) from a sound was provided and until the participant pressed a button
Time Frame
Day 1, 6, and 9
Title
Short-term memory
Description
Measured as number of digits correctly remembered after visual presentation
Time Frame
Day 1, 6, and 9
Title
Gastrointestinal symptoms
Description
Measured on the Gastrointestinal Symptom Rating Score (GSRS) questionnaire (ranging from 0 (no discomfort) to 6 (very severe discomfort)
Time Frame
Day 1-9
Title
Constipation symptoms
Description
Measured on the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire (ranging from 0 (symptom absent) to 4 (very severe).
Time Frame
Day 1-9
Title
Electroencephalography spectral analysis
Description
40 electrodes will be used to record EEG during a period of 5 minutes rest. The results will be used to model connectivity between brain centres as well as the dominating centres of brain. EEG power will be assessed in the Delta, Theta, Alpha, Beta, and Gamma bands between 1 and 70 Hertz. Finally inverse modelling will be conducted to explore the dominating centres of brain activity.
Time Frame
Day 1 and 9
Title
Pain tolerance threshold
Description
Pressure will be applied to the tibial bone and the quadriceps muscle by a handheld pressure algometer. The pain tolerance threshold (measured in kPa) is reached when the participant reports the pain to be intolerable
Time Frame
Day 1 and 9
Title
Conditioned pain modulation
Description
The left hand of the participant is immersed in 2.0 degree (celsius) cold water for up to 2 minutes or until the pain becomes intolerable. The participant is asked to rate the pain on a 10-point Visual Analogue Scale (0 being no pain and 10 being worst imaginable pain) every 10 seconds during the test.
Time Frame
Day 1 and 9
Title
Gastric half emptying time
Description
Analysis of gastric half emptying time after ingestion of a standardized meal measured by MRI
Time Frame
Day 1 and 9
Title
Gastric contraction assessment
Description
Analysis of gastric contraction including amplitude and frequency of contractions after ingestion of a standardized meal measured by MRI
Time Frame
Day 1 and 9
Title
Small bowel motility assessment
Description
Analysis of small bowel motility after ingestion of a standardized meal measured using dynamic MRI images. A semi-automated analysis software enables registration of small bowel motility with the calculation of regional motility maps and quantification of motility indices.
Time Frame
Day 1 and 9
Title
Small bowel water content
Description
Analysis of small bowel water content measured using heavily T2-weighted MRI images
Time Frame
Day 1 and 9
Title
Colon volume
Description
Volumetric quantification of the colon measured using T2-weighted MRI images
Time Frame
Day 1 and 9
Title
Estimated gastrointestinal transit time
Description
Using DIXON images, location of three capsules filled with contrast fluid ingested 24 hours before MRI scan
Time Frame
Day 1 and 9

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Signed informed consent before any study specific procedures Able to read and understand Danish Male or female with an age of 20 years or more The researcher believes that the participant understands what the study entails, are capable of following instructions, can attend when needed, and are expected to complete the study. The investigator will ensure that fertile female participants have a negative pregnancy test before each treatment visit and use contraception during the entity of the study. Opioid naïve (in this study "opioid naïve" is defined as a person who does not have a history of opioid use/addiction. If the opioids were used more than five years before the start of experiment as an analgesic to treat pain post-surgery etc., this person will be considered opioid naïve. If the person has never used opioids to treat pain but has participated in pain studies where opioids were given more than a year before this experiment, this person will be considered opioid naïve) Healthy (assessed by a study-affiliated medical doctor) Exclusion Criteria: Known allergy towards pharmaceutical compounds similar to Dropizol. Participation in other studies within 14 days of first visit (1 year if opioids involved). Expected need of medical/surgical treatment during the study History of psychiatric illness (e.g. mental retardation, schizophrenia, affective disorders (depression), personality disorders or treatment with psychoactive medications) History of substance abuse (e.g. alcohol, nicotine, tetrahydrocannabinol (THC), benzodiazepine, central stimulants and/or opioids) Family history of substance abuse Known increased intracranial pressure Known major stenosis of the intestines Planned MRI within the next 3 months Metal implants or pacemaker Known severe decreased renal function (defined as estimated glomerular filtration rate (eGFR) below 45) Known severe decreased hepatic function (defined as Child-Pugh class B or higher) Treatment with Monoamine oxidase (MAO) inhibitors during the entity of the study Known severe chronic obstructive pulmonary disease (COPD) or acute severe asthma (defined as forced expiratory volume in 1 second (FEV1) below 50 % or acute ongoing exacerbation) Known cor pulmonale Female participants that are lactating Medicine known to affect gastrointestinal motility must not be initiated during the entity of the study Use of any analgesic medication within 48 hours before start as well as for the duration of the study (urine drug test will be performed prior to treatment start). Intake of alcohol within 48 hours before start of study period as well as for the duration of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asbjørn Mohr Drewes
Organizational Affiliation
Aalborg University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data can by provided upon request
IPD Sharing Access Criteria
Researchers who provide a methodological sound proposal

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Opium Tincture Against Chronic Diarrhea - Healthy

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