Condition category
Infections and Infestations
Date applied
11/03/2009
Date assigned
21/04/2009
Last edited
03/02/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.a-wol.net/

Funders

Funder type

Charity

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

Bill & Melinda Gates Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes