Opium Tincture Against Chronic Diarrhea - Patients

Study Overview
=================
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 patients with chronic diarrhea

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 16 patients with chronic diarrhea, we 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.

Official Title
-----------------
Opium Tincture Against Chronic Diarrhea - Patients An Investigator Initiated, Randomized Placebo-controlled, Double-blinded, Clinical Trial

Conditions
-----------------
Chronic Diarrhea

Intervention / Treatment
-----------------
* Drug: Opium tincture
* Drug: Placebo


Participation Criteria
=================
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. Specific underlying pathophysiology has been identified, but targeted treatment (e.g. antibiotics or bile acid sequestrants) and treatment with loperamide has failed. OR No specific underlying pathophysiology has been identified and treatment with loperamide has failed. At least 6 months post-surgery in the gastrointestinal tract No sign of cancer at standard clinical follow-up Chronic diarrhea defined as at least 3 daily bowel movements for the last week 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, major depression) History of substance abuse (e.g. alcohol, THC, benzodiazepine, central stimulants and/or opioids) Family history of substance abuse Known major stenosis of the intestines Known severe decreased renal function (defined as eGFR below 30) Known severe decreased hepatic function (defined as Child-Pugh class B or higher) Treatment with MAO- inhibitors during the entity of the study Severe COPD or acute severe asthma (defined as 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 Treatment with opium tincture during the last month

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active treatment<br>Administration of opium tincture (Dropizol) | Drug: Opium tincture<br>* Self-administration of opium tincture (10 mg/ml) as 3x5 drops on day 1-3, 3x10 drops on days 4-6, and 1x10 drops on day 7 in each study period<br>* Other names: Dropizol;|
| Placebo Comparator: Placebo treatment<br>Administration of placebo (identical to opium tincture in taste and appearance) | Drug: Placebo<br>* Self-administration of placebo (10 mg/ml) as 3x5 drops on day 1-3, 3x10 drops on days 4-6, and 1x10 drops on day 7 in each study period<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel movement frequency | Difference in number of spontaneous bowel movements per day between arms | From day 1 to 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal transit | Difference in hours from ingestion of a wireless motility capsule to expulsion of the capsule during active and placebo treatment | Measurement started on day 4 of each study period until expulsion of the capsule] | 
| Stool consistency | Rated on the Bristol Stool Form Scale (ranging from type 1 - type 7) | From day 1 to 7 in each study period | 
| Pupil diameter | Measured in mm | Day 1, 4 and 7 in each study period | 
| General cognition | Evaluated using the Mini-Mental State Examination | Day 1, 4 and 7 in each study period | 
| Reaction time | Measured in milliseconds (ms) from a sound was provided and until the participant pressed a button | Day 1, 4 and 7 in each study period | 
| Short-term memory | Measured as number of digits correctly remembered after visual presentation | Day 1, 4 and 7 in each study period | 
| Gastrointestinal symptoms | Measured on the Gastrointestinal Symptom Rating Score (GSRS) questionnaire | Day 1, 4 and 7 in each study period | 
| Constipation symptoms | Measured on the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire | Day 1, 4 and 7 in each study period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diarrhea, Gastrointestinal transit