Contact information
Type
Scientific
Primary contact
Prof Achim Hoerauf
ORCID ID
Contact details
Institute of Medical Microbiology
Immunology and Parasitology
University of Bonn
Faculty of Medicine
Sigmund Freud Str.25
Bonn
53105
Germany
+49 (0)228 287 15675
hoerauf@microbiology-bonn.de
Type
Scientific
Additional contact
Prof Ohene Adjei
ORCID ID
Contact details
Kwame Nkrumah University of Science and Technology (KNUST)
and Kumasi Centre of Collaborative Research (KCCR)
University Post Office
Kumasi
-
Ghana
+233 (0)51 60351
oadjei@africaonline.com
Type
Scientific
Additional contact
Dr Alexander Yaw Debrah
ORCID ID
Contact details
Kwame Nkrumah University of Science and Technology (KNUST)
and Kumasi Centre of Collaborative Research (KCCR)
University Post Office
Kumasi
-
Ghana
+233 (0)51 60351
yadebrah@yahoo.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Grant ref: 39284
Study information
Scientific title
Comparison of doxycycline alone vs doxycycline plus rifampicin in their efficacy against onchocerciasis: a randomised double-blind placebo-controlled trial
Acronym
A-WOL Oncho
Study hypothesis
1. To refine existing regimes of drugs with known activity against Wolbachia (doxycycline, rifampicin):
1.1. To provide a shortened treatment period compared to the gold-standard (200mg doxycycline per day for 6 weeks) using the combination of doxycycline and rifampicin.
1.2. To provide a reduction of the daily dosage of doxycycline from 200mg to 100mg.
1.3. To evaluate if the treatment with rifampicin alone has an equivalent effect compared to doxycycline alone.
2. To use immune and metabolite profiling to identify markers of infection and macrofilaricidal activity to provide accurate and sensitive diagnostic tools for individual treatment and control programme monitoring and evaluation.
Added 25/01/2016:
The registration was initiated on 11/03/2009 and finalised on 21/04/2009 after payment was received. Following the prospective submission on 11/03/2009, there were no subsequent changes to the protocol. The recruitment started on 15/03/2009, after initiation of public registration.
Ethics approval
Germany: Ethical Committee, University Clinic Bonn, Faculty of Medicine, Bonn, approved on 11/08/2008
Ghana: Committee on Human Research Publication and Ethics, Kwame Nkrumah University of Science and Technology, Kumasi, approved on 29/07/2008
Study design
Randomised double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Onchocerciasis (Onchocerca volvulus)
Intervention
The participants will be randomised and assigned to one of the following five treatment regimens:
Treatment regimen 1 (n=150):
a. 6 weeks doxycycline 200 mg (2 capsules/day)
b. 6 weeks placebo matching rifampicin (3 or 4 capsules/day)
Treatment regimen 2 (n=100):
a. 6 weeks doxycycline 100 mg (1 capsule/day) plus placebo matching doxycycline 100 mg (1 capsule/day)
b. 6 weeks placebo matching rifampicin (3 or 4 capsules/day)
Treatment regimen 3 (n=100):
a. 3 weeks doxycycline 200 mg followed by 3 weeks placebo (2 capsules/day)
b. 3 weeks rifampicin (10 mg/kg BW per day) followed by 3 weeks placebo (3 or 4 capsules/day)
Treatment regimen 4 (n=100)
a. 6 weeks rifampicin (10 mg/kg BW per day) (3 or 4 capsules/day)
b. 6 weeks placebo matching doxycycline (2 capsules/day)
Treatment regimen 5 (n=50)
a. 6 weeks placebo matching doxycycline (2 capsules/day)
b. 6 weeks placebo matching rifampicin (3 or 4 capsules/day)
Volunteers for this study are recruited based on the inclusion and exclusion criteria and treated directly in their villages (Upper- and Lower Denkyira Districts, Dunkwa on Offin, Central Region; Amansie Central and Adanse South Districts, Ashanti Region). The study-drugs will be distributed ad personam by the research staff and drug intake monitored on a daily basis for 6 weeks.
To assess the skin microfilarial load, skin biopsies are taken pre-treatment, as well as at 6 and 20 months after treatment.
Nodulectomies to assess worm vitality and embryogenesis will be performed 6 and 20 months after the start of drug administration. Onchocercomata will be removed under local anaesthesia in the hospital. Patients will be kept in hospital for one day after operation for observation before being discharged. Wound dressing will continue in the villages until all the wounds are healed.
Intervention type
Drug
Phase
Not Applicable
Drug names
Doxycycline, rifampicin
Primary outcome measure
Rates of nodules (onchocercomata) with normal embryogenesis assessed by histology 6 and 20 months after the start of drug administration.
Secondary outcome measures
1. Evaluation of worm embryogenesis (normal embryos/degenerated embryos/no embryos) assessed by histology from onchocercomata excised 6 and 20 months after the start of drug administration
2. Macrofilaricidal activity of the different treatment arms assessed by histology from onchocercomata excised 20 months after the start of drug administration
3. Reduction or absence of Wolbachia bacteria in adult worms assessed by immunohistology (using anti-Wolbachia antibodies) and polymerase chain reaction (PCR) measured 6 and 20 months after the start of drug administration
4. Microfilarial load in the skin measured pre-treatment as well as 6 and 20 months after the start of drug administration
5. Parasite specific immuno-globulin subclasses and cytokine responses/angiogenesis factors measured pre-treatment as well as 6 and 20 months after the start of drug administration
For all the above mentioned primary and secondary outcome measures: Treatment regimens 2 to 4 will subsequently be tested first for superiority compared to placebo (regimen 5) and second for equivalence to the standard therapy (regimen 1).
Overall trial start date
15/03/2009
Overall trial end date
31/12/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Men and women between 18-55 years
2. Good general health without any clinical condition requiring long-term medication and with normal renal and hepatic laboratory profiles
3. Body weight (BW): 40-70 kg
4. Presence of at least 1 palpable onchocercoma
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
500
Participant exclusion criteria
1. Known intolerance to the study drugs (doxycycline, rifampicin)
2. Pregnancy (if not obvious, all women are tested by dipstick chemistry (ß-hCG), the test will be carried out pre-treatment and every 2 weeks during treatment)
3. Currently breast-feeding
4. History of severe allergic reaction or anaphylaxis
5. History of alcohol or drug abuse
6. Evidence of clinically significant neurological, cardiac, pulmonary, hepatic, metabolic, rheumatologic or renal disease as assessed by history of participants, physical examination, and/or laboratory examinations including blood and urine analyses
7. Laboratory evidence of liver disease (alanine aminotransferase [ALT], gamma-GT greater than 1.25 times the upper limit of normal results as stated by the manufacturer of dipstick tests, Roche)
8. Laboratory evidence of renal disease (serum creatinine greater than 1.25 times the upper limit of normal results as stated by the manufacturer of dipstick tests, Roche)
9. Laboratory evidence of diabetes (urine dipstick chemistry)
10. Behavioural, cognitive or psychiatric disease that, in the opinion of the trial clinician, affects the ability of the participant to understand and comply with the study
11. Severe asthma (emergency room visit or hospitalisation)
12. Undergone splenectomy
13. Participation in other drug trials concurrent with this study
14. Any other condition that, in the opinion of the investigator (trial clinician), would risk the safety or rights of a participant in the trial or would render the subject unable to comply with the protocol
Recruitment start date
15/03/2009
Recruitment end date
28/04/2009
Locations
Countries of recruitment
Ghana
Trial participating centre
University of Bonn
Bonn
53105
Germany
Sponsor information
Organisation
Liverpool School of Tropical Medicine (UK)
Sponsor details
c/o Prof Mark Taylor
Pembroke Place
Liverpool
L3 5QA
United Kingdom
+44 151 705 3100
mark.taylor@liverpool.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Bill and Melinda Gates Foundation
Alternative name(s)
बिल एंड मिलिंडा गेट्स फाउंडेशन, Bill & Melinda Gates Foundation, Gates Foundation, 比尔及梅琳达·盖茨基金会, BMGF, B&MGF
Funding Body Type
private sector organisation
Funding Body Subtype
Trusts, charities, foundations (both public and private)
Location
United States of America
Results and Publications
Publication and dissemination plan
There will be a publication of the results; a manuscript is currently in preparation
Intention to publish date
Participant level data
Available on request
Basic results (scientific)
Publication list