A randomized trial of disulfiram and zinc administered together to treat diarrhea caused by Entamoeba histolytica
| ISRCTN | ISRCTN15356736 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15356736 |
| Secondary identifying numbers | IRB202501125 |
- Submission date
- 22/09/2025
- Registration date
- 24/09/2025
- Last edited
- 24/09/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Amebiasis, caused by Entamoeba histolytica, is a significant global health concern and one of the leading causes of severe diarrhea and death from parasitic infections worldwide. Despite its prevalence, treatment options are limited to a single class of drugs, posing a public health risk in the event of drug resistance or intolerable side effects. This study will evaluate the safety and effectiveness of oral disulfiram combined with a nutritional zinc supplement as a novel treatment for symptomatic E. histolytica diarrhea.
Who can participate?
Ambulatory patients aged 18 years and older with symptomatic diarrhea due to E. histolytica.
What does the study involve?
Participants who meet all eligibility criteria and consent to participation will be randomly allocated to receive either low dose disulfiram (250 mg) daily plus 50 mg zinc gluconate thrice daily x 10 days; high dose disulfiram (500 mg) daily plus 50 mg zinc gluconate thrice daily x 10 days or the active control metronidazole (500 mg) thrice daily x 10 days). Participants will be followed for safety and effectiveness outcomes.
What are the possible benefits and risks of participating?
Participants will benefit from close monitoring throughout the study. Similar patients with amebic colitis may benefit in the future from alternative therapies if resistance to metronidazole develops or there is an intolerance to metronidazole.
Participants may experience side effects from the study treatment, including nausea, liver toxicity, or allergic reactions from the study drug. Severe reactions can occur if alcohol is consumed during treatment. Blood draws may cause temporary pain, bruising, or lightheadedness. There is also a small risk of a breach of confidentiality, though strict data protection measures will be in place to minimize this.
Where is the study run from?
The study is an international study that will be conducted in Manila, Philippines.
When is the study starting and how long is it expected to run for?
August 2025 to August 2029
Who is funding the study?
National Institutes of Health (USA), grant R34AI165304
Who is the main contact?
Debbie-Ann Shirley, dshirley1@ufl.edu
Contact information
Public, Scientific, Principal Investigator
1600 SW Archer Road
HD214
Gainesville
32610
United States of America
| Phone | +1 (0)3522948591 |
|---|---|
| dshirley1@ufl.edu |
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Disulfiram for Entamoeba histolytica Enteric Diarrhea (DEED) trial |
| Study acronym | DEED |
| Study objectives | Amebiasis, caused by Entamoeba histolytica, is a leading cause of severe diarrhea and death from parasitic infection worldwide. Globalization, immigration, travel to and from endemic areas, and sexual practices are contributing to re-emergence in developed countries. There is only one drug class available for treatment, which is a major public health concern as there is no option if resistance or intolerable side effects were to develop. Treatment options for parasitic infections remain limited, hence identification of new anti-parasitic drugs is priority. We found that zinc ditiocarb, a metabolite of the inexpensive, globally available, oral FDA-approved drug disulfiram, was 1000-fold more potent than metronidazole and was an effective anti- amebic agent in pre-clinical animal studies of amebic colitis. Zinc ditiocarb is safely given as disulfiram plus nutritional zinc supplement. We propose to test the hypothesis that oral disulfiram plus zinc supplement effectively treats Entamoeba histolytica diarrhea. If our hypothesis holds true, the proposed trial could result in an innovative repurposed indication for the first new drug treatment for amebiasis in over 60 years. The primary safety objective is: 1.1. To evaluate the safety and clinical acceptability of a 10-day course of oral disulfiram once daily plus zinc three times daily in participants with diarrhea due to E. histolytica. The primary efficacy objective is: 1.2. To examine the efficacy of a 10-day course of disulfiram once daily plus zinc three times daily in treating participants with diarrhea due to E. histolytica. The endpoint will be proportion with resolution of diarrhea (no loose stools for 24 hours) after a 10-day course. The secondary efficacy objective is: 2. To determine the efficacy of disulfiram in eradicating infection in participants with diarrhea due to E. histolytica. |
| Ethics approval(s) |
Not yet submitted, University of Florida Institutional Review Board (Address not provided, Gainesville, 32610, United States of America; Telephone number not provided; Email not provided), ref: Reference number not provided |
| Health condition(s) or problem(s) studied | Symptomatic diarrhea due to E. histolytica |
| Intervention | Participants who meet all eligibility criteria and consent to participation will be randomized to receive either low dose disulfiram (250 mg) daily plus 50 mg zinc gluconate thrice daily x 10 days; high dose disulfiram (500 mg) daily plus 50 mg zinc gluconate thrice daily x 10 days or the active control metronidazole (500 mg) thrice daily x 10 days). Participants will be followed for safety and efficacy outcomes. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Disulfiram plus 50 mg zinc gluconate |
| Primary outcome measure | Primary safety endpoint: The proportion of participants experiencing a grade 3 or greater adverse event during a 10-day course of study treatment Primary efficacy endpoint: The proportion of participants with resolution of diarrhea (no loose stools for 24 hours i.e. Bristol type 6-7) at end of therapy after a 10-day course of study treatment course |
| Secondary outcome measures | Secondary efficacy endpoint: The proportion of participants with negative stool microscopy at end of therapy after a 10-day course of study treatment course |
| Overall study start date | 09/08/2025 |
| Completion date | 09/08/2029 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 204 |
| Key inclusion criteria | 1. Age 18–65 years inclusive at enrollment in good health, with diarrhea and microbiologically confirmed E. histolytica infection 2. Willing/ able to give informed consent to be enrolled in and comply with trial procedures follow-up 3. Willing to abstain from alcohol ingestion while on therapy through 28 days 4. For females of reproductive potential, agreement to use highly effective contraception through 28 days |
| Key exclusion criteria | 1. Hypotension or shock 2. Intestinal obstruction, including megacolon and moderate to serve ileus 3. Acute abdomen 4. Admitted to hospital or intensive care unit atenrolmentt 5. Inability to tolerate oral medication 6. Other suspected etiology for diarrhea e.g. other enteric pathogen, other intestinal disease 7. Pregnant and/ or breastfeeding women 8. Consumption of alcohol within 48 hours of enrollment 9. History of alcohol or substance use disorder 10. History of psychosis 11. Severe myocardial dysfunction 12. History of chronic liver disease 13. History of end stage renal disease 14. Prolonged prothrombin time 15. Concomitant treatment with theophylline or warfarin 16. Concomitant use of phenytoin 17. Concomitant use of isoniazid 18. Concomitant use of bictegravir, cabotegravir, dolutegravir, or raltegravir 19. Concomitant treatment with prednisone 40 mg or more daily [or equivalent corticosteroid] 20. Exposure to ethylene dibromide 21. History of known sensitivity or allergic reaction to disulfiram 22. History of known sensitivity or allergic reaction to metronidazole or nitroimidazole derivates 23. History of rubber contact dermatitis 24. Concurrent participation in another investigational trial within the previous 30 days 25. Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol |
| Date of first enrolment | 09/08/2026 |
| Date of final enrolment | 09/08/2028 |
Locations
Countries of recruitment
- Philippines
Study participating centre
Manila
Metro Manila 1000
Philippines
Sponsor information
University/education
1600 SW Archer Road
Gainesville
32610
United States of America
| Website | https://ufhealth.org/ |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Institutos Nacionales de la Salud, US National Institutes of Health, NIH
- Location
- United States of America
Results and Publications
| Intention to publish date | 28/09/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
23/09/2025: Study's existence confirmed by the Department of Health and Human Services.
