Contact information
Type
Scientific
Primary contact
Prof Achim Hoerauf
ORCID ID
Contact details
Institute of Medical Microbiology
Immunology and Parasitology (IMMIP)
University of Bonn
Faculty of Medicine
Sigmund Freud str.26
Bonn
53105
Germany
+49 (0)228 287 5675
hoerauf@parasit.meb.uni-bonn.de
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
EC CONTRACT IC-A4-CT 2002-10051
Study information
Scientific title
Acronym
WOLBACHFIL
Study hypothesis
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
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
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
Condition
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 names
1. Doxycycline
2. Ivermectin
3. Albendazole
Primary outcome measures
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
Secondary outcome measures
Reduction in adverse reaction to ivermectin treatment
Overall trial start date
01/12/2002
Overall trial end date
31/05/2005
Reason abandoned
Eligibility
Participant 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.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
240
Participant 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
Recruitment start date
01/12/2002
Recruitment end date
31/05/2005
Locations
Countries of recruitment
Ghana
Trial participating centre
Institute of Medical Microbiology
Bonn
53105
Germany
Sponsor information
Organisation
European Commission
Sponsor details
European Commission
Research Directorate-General
Rue de la Loi 200
Bruxelles
B-1049
Belgium
+32 (0)2 299 1111
rtd-inco-projects@cec.eu.int
Sponsor type
Other
Website
Funders
Funder type
Government
Funder name
European Commission
Alternative name(s)
EC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary