Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202403467543150 Date of Registration: 13/03/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Losartan for Individuals With Epilepsy in Zambia
Official scientific title Losartan for Individuals With Epilepsy in Zambia
Brief summary describing the background and objectives of the trial Epilepsy is the most common chronic neurological disease worldwide, affecting approximately 0.5-0.8% of the global population, 80% of whom reside in low- and middle- income countries (LMICs). In many LMICs, including Zambia, fewer than 20% of individuals with epilepsy are treated with anti-seizure medications (ASMs). Major reasons include the lack of resources and erratic supply of drugs, the high cost of new generation ASMs, and stigma toward those with epilepsy. We propose to investigate the repurposing of losartan, a widely available low-cost medication used to treat high blood pressure, as add-on therapy for the treatment of patients with drug-resistant epilepsy. The open-label clinical trial based at the Kakumbi Rural Health Centre in Mfuwe, in the Eastern Province of Zambia. We will recruit 30 participants aged 18 to 70 who continue to experience seizures while receiving carbamazepine and phenobarbital - the only ASMs provided by the Zambian Ministry of Health. Participants will be monitored for 6 months on their existing medication to document seizure frequency and comorbidities. Losartan will then be prescribed in addition to the ASMs and monitoring will continue for 6 months. A 50% reduction in seizures will be considered a success. A similar clinical trial is currently being conducted in Israel and data will be available for comparison. Primary Aim: To evaluate any change in seizure frequency (with a decline in 50% or more of participants considered a success) or blood pressure following the addition of losartan to participants’ ASMs, and document changes in their quality of life. Study Aim 2. Evaluate the effect of losartan on brainwave activity observed in patients with epilepsy based on quantitative analysis of EEG results from before and after addition of losartan to ASMs. Study Aim 3: Evaluate drug-drug interaction between ASMs and losartan based on 6 months’ add-on, as well as monitoring hCG levels, kidney and liver function.
Type of trial Non-Randomised
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Epilepsy
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 08/03/2024
Actual trial start date
Anticipated date of last follow up 31/01/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Single Group Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Added Dosage of Losartan For the 12 month duration of the trial, participants will continue to take phenobarbital or carbamazepine, which they must have been prescribed by their general practitioner and adhered to at least three months prior to the study. Dosage will vary between participants and may be increased at the discretion of their general practitioner. Maximum dosages, respectfully, are 800 mg/day for Carbamazepine and 200mg/day for Phenobarbital. Participants who remain in the study for months 7-12 will be prescribed 50 mg of Losartan per day to be taken in addition to CBZ or PB. If no improvement in seizure frequency or duration is seen, the dosage of losartan may be increased to 75 mg/day. Participants will be continue taking their prescribed medication (CBZ/PB) for the full duration of the study (12 months). Participants will be given Losartan as an add-on medication for the last 6 months of the study to see if it improves the efficiency of CBZ/PB. If at the end of the project, participants request to continue taking Losartan thanks to improved quality of life, it will be provided for free by local NGO The Mfuwe Epilepsy Foundation. Blood-pressure monitoring will be performed weekly during the first month of treatment with losartan, and every four weeks thereafter. If a participant chooses to withdraw from the study during months 7-12 of their participation while taking 50 or 75 mg of losartan, they will be gradually tapered off the medication to avoid any sudden increase of blood pressure. 30
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Participants must be between the ages of 18 and 70 years and previously diagnosed with epilepsy. - Participants must have experienced seizures for at least the preceding 3 months despite prior and ongoing therapy with PB and/or CBZ. - Participants are to have at least one seizure per 28 days on average, with no seizure-free period longer than 28 days during the 3 months before enrolment, as well as during the 6-month baseline period. - Participants must have taken a therapeutic dosage regimen of PB or CBZ in the 3-months before enrolment and a stable therapeutic dosage during the 6-months baseline period. - Female participants who are pregnant, breast-feeding, or of childbearing potential and not using approved methods of contraception. - Participants with a history of chronic alcohol or drug abuse. - Participants with any medical condition that might jeopardize the patient’s health or compromise the patient’s ability to participate in this trial including abnormal liver function; diastolic blood pressure <50 mm Hg or pulse <50 or >110 beats per minute after 3 minutes in a sitting position; history of severe anaphylactic reaction or serious blood dyscrasias; nonepileptic events, including psychogenic seizures; or any other clinically significant condition. Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 70 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 11/12/2023 ERES Converge
Ethics Committee Address
Street address City Postal code Country
Joseph Mwilwa Road Lusaka 10100 Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Evaluate the efficacy of losartan as an add-on treatment for patients with epilepsy. From the 6-month baseline to completion of the 6-month trial on losartan, the study’s clinical coordinator will be visited by participants at the Kakumbi Rural Health Centre to monitor (1) seizures’ semiology and frequency using a standard questionnaire filled monthly, and daily seizure diaries which will be completed by the patients or their caregivers; (2) blood pressure will be measured weekly during the first month of treatment with losartan and monthly for the five months thereafter; (3) quality of life and stigma will be measured using standard questionnaires filled before and after each 6-month monitoring period; and (4) side effects of ASMs and losartan will be monitored monthly using standard questionnaires and bloodwork. After 6 months of patients taking losartan as an add-on to phenobarbital or carbamazepine.
Secondary Outcome Evaluate the effect of losartan on EEG features which are observed in patients with epilepsy. This would be completed by repeating EEG examinations (20-minute duration) upon recruitment, after 6 months baseline on phenobarbital and/or carbamazepine, and after 6 months’ add-on prescription of losartan. The EEG results will be read by an experienced epileptologist. Quantitative analysis for abnormal activity and interictal epileptiform activity will be done as established by our group. Months 1, 6, and 12 of participants time in the study.
Secondary Outcome Evaluate the effect of losartan on the drug levels of ASMs taken by the patients. Bloodwork will be taken w2eekly during the first month of treatment with losartan and monthly from months 2 to 6 with losartan as add-on treatment to evaluate and/or rule out its potential interactions with patients’ levels of phenobarbital and/or carbamazepine. The kidney and liver function, as well as hCG levels (for women at childbearing age), will also be measured. Months 7 - 12
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kakumbi Rural Health Centre PO Box 511297 Mambwe District Eastern Province Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
Cures Within Reach 1130-134 N La Salle St Chicago 60602 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Cures Within Reach 1130-134 N La Salle St Chicago 60602 United States of America Funding Agency
Secondary Sponsor Dalhousie University Department of Medical Neuroscience 5850 College Street, PO Box 15000 Halifax B3H 4R2 Canada University
COLLABORATORS
Name Street address City Postal code Country
Dr. Alon Friedman 5850 College Street, PO Box 15000 Halifax B3H 4R2 Canada
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Stanley Zimba stanpaulzimba@yahoo.co.uk +260977437082 Ridgeway Campus
City Postal code Country Position/Affiliation
Lusaka Zambia National Coordinator at University Teaching Hospital
Role Name Email Phone Street address
Public Enquiries Andrew Malunga andrewmalunga37@gmail.com 260979899923 Kakumbi Rural Health Centre, PO Box 511297
City Postal code Country Position/Affiliation
Mambwe District Eastern Province Zambia Nurse
Role Name Email Phone Street address
Scientific Enquiries Alon Friedman alon.friedman@dal.ca +19024943725 5850 College Street
City Postal code Country Position/Affiliation
Halifax B3H 4R2 Canada Professor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The primary objective of our study is to examine whether losartan may reduce seizure frequency as an add-on to prescriptions of phenobarbital or carbamazepine. We are committed to promoting transparency and advancing scientific knowledge through the responsible sharing of individual participant data (IPD). All shared data will be de-identified and stripped of any personally identifiable information to ensure anonymity. Informed Consent Form,Study Protocol We aim to share de-identified participant data upon the completion of our research and publication of the primary outcomes. It will be available for access upon for 5 years. Qualified researchers will be required to submit a formal request to the Principal Investigator. Applicants must specify the intended purpose for accessing the individual participant data and ensure that it aligns with ethical and scientific standards. A research proposal must be submitted, detailing the study's objectives, methods and expected outcomes, as well as proof of approval from a research ethics board. The applicants must show that they have established stringent data security and privacy protocols that they will adhere to, with clearly defined restrictions on data handling and dissemination. Lastly, any publication of findings should acknowledge the original data source.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information