Antibiotic targeting of Wolbachia endosymbiotic bacteria as a new approach to the treatment of filarial (Wuchereria bancrofti) infection and disease

ISRCTN	ISRCTN56578422
DOI	https://doi.org/10.1186/ISRCTN56578422
Protocol serial number	EC CONTRACT IC-A4-CT 2002-10051
Sponsor	European Commission
Funder	European Commission

Submission date: 10/02/2006
Registration date: 22/02/2006
Last edited: 25/09/2009

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 (IMMIP)
University of Bonn
Faculty of Medicine
Sigmund Freud str.26
Bonn
53105
Germany

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

Study information

Primary study design	Interventional
Study design	Randomised double-blind placebo-controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	WOLBACHFIL
Study objectives	Wolbachia are symbiotic endobacteria in filarial nematodes that have recently emerged as targets for an 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 was: 1. To obtain the optimal regimen with anti-Wolbachia antibiotics leading to Wolbachia depletion and sterilization or killing of adult worms in human filariasis. 2. To analyze the role of Wolbachia in inflammatory processes which lead to disease manifestations (hydrocele, lymphedema, acute episodes of lymphangitis) 3. To investigate the role of Wolbachia release by microfilaricidal therapy in the induction of side effects. In their combination, the studies will allow us to assess the role of Wolbachia in the pathogenesis and as targets for the long-needed second punch for sustained interruption of transmission.
Ethics approval(s)	Ethical clearance has been obtained from the Liverpool School of Tropical Medicine Research Ethics Committee on 06/12/2001, reference number 01.74 for the whole EC contract and from the Committee on Human Research Publications and Ethics, School of Medical Sciences, University of Science and Technology, Kumasi, Ghana on 20/01/2003
Health condition(s) or problem(s) studied	Lymphatic filariasis due to infection with Wuchereria bancrofti
Intervention	Study drugs and treatment regimens: 1. 200 mg doxycycline per day orally for six weeks plus a single dose of ivermectin (150 µg/kg) plus albendazole (400 mg), four months after the start of doxycycline administration 2. Placebo matching doxycycline orally for six weeks plus a single dose of ivermectin (150 µg/kg) plus albendazole (400 mg), four months after the start of doxycycline-placebo administration 3. 200 mg doxycycline per day orally for three weeks plus a single dose of ivermectin (150 µg/kg) plus albendazole (400 mg), four months after the start of doxycycline administration 4. Placebo matching doxycycline orally for three weeks plus a single dose of ivermectin (150 µg/kg) plus albendazole (400 mg), four months after the start of doxycycline-placebo administration
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	1. Doxycycline 2. Ivermectin 3. Albendazole
Primary outcome measure(s)	1. Depletion of Wolbachia (gene copies per Mf by quantitative Polymerase Chain Reaction [PCR]) 2. Subsequent decline in microfilaraemia (according to Mf half-life) due to inferred sterility of adult worms 3. Macrofilaricidal effects, as assessed by ultrasonography and by reduction of circulating filarial antigen in serum 4. Decrease in size and grade of chronic pathology and frequency of acute inflammatory episodes
Key secondary outcome measure(s)	Reduction in adverse reaction to ivermectin treatment
Completion date	31/05/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	50 Years
Sex	All
Target sample size at registration	240
Key inclusion criteria	For all participants: subjects of both sexes, aged 18-50 years, who have given informed consent (written or thumb print) were evaluated. Minimum criteria was body weight >40 kg. Participants were only included in case they met the following criteria: normal renal and hepatic laboratory profiles for aspartate aminotransferase (AST) (0-40 IU/l), alanine aminotransferase (ALT) (0-45 IU/l), creatinine 53-126 µmol/l) as measured by dipstick chemistry. For microfilaraemic participants: minimum criteria was microfilarial (Mf) counts >50 Mf/ml (finger pricks taken from night blood between 8 and 10 p.m., counted through a blood counting chamber, e.g. Sedgewick®. For patients with early or chronic signs of disease: microfilaraemic or amicrofilaraemic, clinical manifestation of hydrocele and/or lymphedema.
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	01/12/2002
Date of final enrolment	31/05/2005

Locations

Countries of recruitment

Germany
Ghana

Study participating centre

Institute of Medical Microbiology

Bonn
53105
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan