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 |
| Secondary identifying numbers | EC CONTRACT IC-A4-CT 2002-10051 |
- 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
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 |
|---|---|
| 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 | |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 1. Doxycycline 2. Ivermectin 3. Albendazole |
| Primary outcome measure | 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 study start date | 01/12/2002 |
| Completion date | 31/05/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 50 Years |
| Sex | Both |
| Target number of participants | 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
53105
Germany
Sponsor information
European Commission
Other
Other
European Commission
Research Directorate-General
Rue de la Loi 200
Bruxelles
B-1049
Belgium
| Phone | +32 (0)2 299 1111 |
|---|---|
| rtd-inco-projects@cec.eu.int | |
| Website | http://www.europa.eu.int |
"ROR" |
https://ror.org/00k4n6c32 |
Funders
Funder type
Government
European Commission
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- European Union, Comisión Europea, Europäische Kommission, EU-Kommissionen, Euroopa Komisjoni, Ευρωπαϊκής Επιτροπής, Европейската комисия, Evropské komise, Commission européenne, Choimisiúin Eorpaigh, Europskoj komisiji, Commissione europea, La Commissione europea, Eiropas Komisiju, Europos Komisijos, Európai Bizottságról, Europese Commissie, Komisja Europejska, Comissão Europeia, Comisia Europeană, Európskej komisii, Evropski komisiji, Euroopan komission, Europeiska kommissionen, EC, EU
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 |
