Comparison of doxycycline alone vs doxycycline plus rifampicin in their efficacy against onchocerciasis

ISRCTN	ISRCTN68861628
DOI	https://doi.org/10.1186/ISRCTN68861628
Secondary identifying numbers	Grant ref: 39284

Submission date: 11/03/2009
Registration date: 21/04/2009
Last edited: 03/02/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Achim Hoerauf
Scientific

Institute of Medical Microbiology, Immunology and Parasitology
University of Bonn
Faculty of Medicine
Sigmund Freud Str.25
Bonn
53105
Germany

Phone	+49 (0)228 287 15675
Email	hoerauf@microbiology-bonn.de

Prof Ohene Adjei
Scientific

Kwame Nkrumah University of Science and Technology (KNUST), and Kumasi Centre of Collaborative Research (KCCR)
University Post Office
Kumasi
-
Ghana

Phone	+233 (0)51 60351
Email	oadjei@africaonline.com

Dr Alexander Yaw Debrah
Scientific

Kwame Nkrumah University of Science and Technology (KNUST), and Kumasi Centre of Collaborative Research (KCCR)
University Post Office
Kumasi
-
Ghana

Phone	+233 (0)51 60351
Email	yadebrah@yahoo.com

Study information

Study design	Randomised double-blind placebo-controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Comparison of doxycycline alone vs doxycycline plus rifampicin in their efficacy against onchocerciasis: a randomised double-blind placebo-controlled trial
Study acronym	A-WOL Oncho
Study objectives	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(s)	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
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	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 study start date	15/03/2009
Completion date	31/12/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	55 Years
Sex	Both
Target number of participants	500
Key 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
Key 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
Date of first enrolment	15/03/2009
Date of final enrolment	28/04/2009

Locations

Countries of recruitment

Germany
Ghana

Study participating centre

University of Bonn

Bonn
53105
Germany

Sponsor information

Liverpool School of Tropical Medicine (UK)
University/education

c/o Prof Mark Taylor
Pembroke Place
Liverpool
L3 5QA
England
United Kingdom

Phone	+44 151 705 3100
Email	mark.taylor@liverpool.ac.uk
Website	http://www.a-wol.net/
"ROR"	https://ror.org/03svjbs84

Funders

Funder type

Charity

Bill and Melinda Gates Foundation
Government organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
Location: United States of America

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	There will be a publication of the results; a manuscript is currently in preparation
IPD sharing plan