Opium Tincture Against Chronic Diarrhea - Patients

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Diarrhea
• Intervention / Treatment: Drug: Opium tincture; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
  • Aarhus, Denmark
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active treatment; Administration of opium tincture (Dropizol)	Drug: Opium tincture; 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; Other Names: Dropizol
Placebo Comparator: Placebo treatment; Administration of placebo (identical to opium tincture in taste and appearance)	Drug: Placebo; 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

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

Collaborators and Investigators

• Sponsor: Asbjørn Mohr Drewes
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Asbjørn Mohr Drewes, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Actual): December 21, 2023
• Study Completion (Actual): December 21, 2023

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 10, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Diarrhea; Gastrointestinal transit
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Gastrointestinal Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Antidiarrheals; Opium
• Other Study ID Numbers: Dropizol_patients; 2020-000396-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data can by provided upon request
• IPD Sharing Access Criteria: Researchers who provide a methodological sound proposal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No