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
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
1/81 306
Study information
Scientific title
Wolbachia endobacteria in filarial infections - exploring their usefulness as targets for novel chemotherapies that are anti-filarial and improve lymphoedema: a randomised double blind placebo-controlled trial
Acronym
Study hypothesis
Filarial infections belong to the major diseases in sub-Saharan Africa and are strongly associated with poverty. At present, World Health Organization (WHO) led control activities in Africa mainly rely on mass administration of microfilaricidal drugs, with a measure of success. However, it has become clear that new, complementary therapies, ideally being macrofilaricidal, must be developed for sustainable control.
In lymphatic filariasis (LF), there is the additional need to deliver new therapies for lymphatic pathology, i.e. lymphoedema and urogenital pathology such as hydrocele and lymphocele, which are not targeted by current mass drug administrations. Depletion of Wolbachia essential endosymbionts of filariae with doxycycline, an approach established by our group, resulted in macrofilaricidal activity in LF. The present study hypothesises that Wolbachia also play a major role in inducing and maintaining lymphatic pathology, and that doxycycline may therefore improve lymphoedema.
The aim of this project is:
1. To analyse to what extent lymphoedema is caused by Wolbachia. To this, the Wolbachia-depleting antibiotic doxycycline will be compared with amoxicillin, which does not target Wolbachia but only opportunistic exogenous bacteria that may worsen lymphoedema.
2. To analyse the role of Wolbachia in the systemic immune responses in lymphoedema patients, by comparing immune responses before and after Wolbachia depletion
Ethics approval
The Committee on Human Research Publication and Ethics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana approved on 25th November 2005
Study design
Randomised double blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Lymphatic filariasis (Wuchereria bancrofti)
Intervention
Study drugs and treatment regimens:
1. 200 mg/day doxycycline for 6 weeks
2. 1000 mg/day amoxicillin for 6 weeks
3. Placebo for 6 weeks
Contact details for Joint Principal Investigators:
Professor Ohene Adjei
Kwame Nkrumah University of Science and Technology (KNUST), and Kumasi Centre of Collaborative Research (KCCR)
University Post Office
Kumasi, Ghana
Tel: + 233 51 60351
Fax: + 233 51 62017
E-mail: oadjei@africaonline.com
Dr Alexander Yaw Debrah
Kwame Nkrumah University of Science and Technology (KNUST), and Kumasi Centre of Collaborative Research (KCCR)
University Post Office
Kumasi, Ghana
Tel: + 233 51 60351
Fax: + 233 51 62017
E-mail: yadebrah@yahoo.com
Intervention type
Drug
Phase
Phase II
Drug names
Doxycycline, amoxicillin
Primary outcome measure
Reduction of the stage of lymphoedema and number of acute attacks, measured pre-treatment as well as 3 months, 12 months and 24 months after the start of drug administration
Secondary outcome measures
1. Reduction in circulating filarial antigen levels as a measure of a macrofilaricidal effect of doxycycline
2. Change in systemic immune responses
All measured pre-treatment as well as 3 months, 12 months and 24 months after the start of drug administration.
Overall trial start date
01/12/2005
Overall trial end date
30/03/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Men and women aged between 18 - 60 years
2. Resident in the village for five years or more
3. Clinical stage of lymphoedema (1 - 5) of at least one extremity
4. Good general health without any clinical condition requiring long-term medication
5. Minimum body weight 40 kg
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
150
Participant exclusion criteria
1. Pregnancy (if not obvious all women are tested by dipstick chemistry: beta-human chorionic gonadotrophin [BhCG])
2. Currently breast-feeding
3. Evidence of clinically significant neurological, cardiac, pulmonary, hepatic, rheumatological, or renal disease by history, physical examination, and/or laboratory tests
4. Behavioural, cognitive or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study protocol
5. Laboratory evidence of liver disease (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and/or gamma-glutamyl transferase [gGT] greater than 1.25 times the upper limit of normal of the testing laboratory)
6. Laboratory evidence of renal disease (serum creatinine greater than 1.25 times the upper limit of normal of the testing laboratory)
7. Other condition that, in the opinion of the investigator, would jeopardise the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol
8. Volunteer has abused alcohol or illicit drugs during the past 6 months by history
9. History of severe allergic reaction or anaphylaxis
10. Intolerance to doxycycline or amoxicillin
Recruitment start date
01/12/2005
Recruitment end date
30/03/2009
Locations
Countries of recruitment
Ghana
Trial participating centre
Institute of Medical Microbiology, Immunology and Parasitology
Bonn
53105
Germany
Sponsor information
Organisation
Volkswagen Foundation (VolkswagenStiftung) (Germany)
Sponsor details
c/o Dr. Detlev Hanne
Division Natural and Engineering Sciences
Medicine
Kastanienallee 35
Hannover
30519
Germany
+49 (0)511 8381 0
info@volkswagenstiftung.de
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
Volkswagen Foundation (VolkswagenStiftung) (Germany) (ref: 1/81 306)
Alternative name(s)
VolkswagenStiftung
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
Germany
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
Basic results (scientific)
Publication list
1. 2012 results in www.ncbi.nlm.nih.gov/pubmed/22610930
Publication citations
-
Results
Mand S, Debrah AY, Klarmann U, Batsa L, Marfo-Debrekyei Y, Kwarteng A, Specht S, Belda-Domene A, Fimmers R, Taylor M, Adjei O, Hoerauf A, Doxycycline improves filarial lymphedema independent of active filarial infection: a randomized controlled trial., Clin. Infect. Dis., 2012, 55, 5, 621-630, doi: 10.1093/cid/cis486.