Antibiotic targeting of wolbachia endosymbiotic bacteria as a new approach to the treatment of filarial (Onchocerca Volvulus) infection and disease

ISRCTN	ISRCTN71141922
DOI	https://doi.org/10.1186/ISRCTN71141922
Secondary identifying numbers	EC contract IC-A4-CT 2002-10051 (WP 1)

Submission date: 02/06/2006
Registration date: 06/07/2006
Last edited: 09/05/2019

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Achim Hoerauf
Scientific

Director of the Institute of Medical Microbiology Immunology and Parasitology (IMMIP)
University of Bonn
Faculty of Medicine
Sigmund Freud Str.25
Bonn
53105
Germany

Phone	+49 (0)228 287 5675
Email	hoerauf@parasit.meb.uni-bonn.de

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
Scientific title	Antibiotic targeting of wolbachia endosymbiotic bacteria as a new approach to the treatment of filarial (Onchocerca Volvulus) infection and disease
Study acronym	WOLBACHFIL
Study objectives	Wolbachia are symbiotic endobacteria in filarial nematodes that have recently emerged as targets for improved chemotherapy of filariasis by tetracycline antibiotics, with the potential to close the gap left open in current mass treatment programs. The purpose of this project is: 1. To define the minimum regimen of anti-wolbachia drug doxycycline needed to achieve depletion of wolbachia and a complete sterilization of adult female worms in onchocerciasis, as well as sustained amicrofilaraemia in combination with ivermectin 2. To verify or reject the macrofilaricidal effect of doxycycline 3. To investigate the role of wolbachia-release by microfilaricidal therapy in the induction of side effects. The study will allow us to assess the role of wolbachia in pathogenesis and as targets for the long-needed second punch for sustained amicrofilaraemia and interruption of transmission.
Ethics approval(s)	Ethical approval has been obtained from the Liverpool School of Tropical Medicine Research Ethics Committee dated 06/12/2001, reference number: 01.74 for the whole EC contract and also from the Committee on Human Research Publications and Ethics, School of Medical Sciences, University of Science and Technology, Kumasi, Ghana dated 20/01/2003)
Health condition(s) or problem(s) studied	Onchocerciasis (river blindness)
Intervention	200 mg/day Oral doxycycline or matching placebo for six weeks versus four weeks; 150 mg/kg oral single dose ivermectin or matching placebo four months post-commencement of doxycycline treatment. Added as of 13/04/2007: 200 was an erroneous copy-paste from an older version of the study protocol which got down-scaled by the Ethics Committee during the process of ethical clearance - the final study protocol version contained three treatment arms with 25 participants each, therefore a total number of 75 participants.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Doxycycline, ivermectin
Primary outcome measure	1. Sustained amicrofilaraemia in doxycycline- and ivermectin-treated patients compared with ivermectin-treated patients as assessed by levels of microfilaridermia in skin biopsies at 5,15 and 21 months 2. Macrofilaricidal (curative) effects of doxycycline treatment as assessed by immunohistology, polymerase chain reaction (PCR) and ultrasonography at 5, 15 and 21 months
Secondary outcome measures	Reduction in adverse reaction to ivermectin treatment
Overall study start date	01/08/2003
Completion date	30/11/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	50 Years
Sex	Both
Target number of participants	200 (75 as of 13/04/07 - see interventions field)
Total final enrolment	67
Key inclusion criteria	All male or female subjects, aged 18-50 years, who have given informed consent (written or thumb print) were evaluated. Minimum body weight criteria is >40 kg. Participants were then included only if they met the following criteria: 1. Normal renal and hepatic laboratory profiles for aspartate aminotransferase (AST) (0-40 IU/l), alanine aminotransferase (ALT) (0-45 IU/l) 2. Creatinine 53-126 µmol/l as measured by dipstick chemistry 3. More than two palpable onchocercomas 4. Microfilarial (Mf) counts >10 Mf/mg (skin biopsies)
Key exclusion criteria	1. Pregnancy (pregnancy test) 2. Lactation 3. Intolerance to ivermectin or doxycycline 4. Chronic diseases 5. Alcohol or drug abuse 6. Anti-filarial therapy within the last two years
Date of first enrolment	01/08/2003
Date of final enrolment	30/11/2005

Locations

Countries of recruitment

Germany
Ghana

Study participating centre

Director of the Institute of Medical Microbiology Immunology and Parasitology (IMMIP)

Bonn
53105
Germany

Sponsor information

European Commission (Belgium)
Government

European Commission
Research Directorate-General
Rue de la Loi 200
Bruxelles
B-1049
Belgium

Phone	+32 (0)2 299 1111
Email	rtd-inco-projects@cec.eu.int
Website	http://www.europa.eu.int
"ROR"	https://ror.org/00k4n6c32

Funders

Funder type

Government

European Commission (EC) contract (Belgium) (ref: IC-A4-CT2002-10051)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2008	09/05/2019	Yes	No

Editorial Notes

09/05/2019: Publication reference and total final enrolment added.