Wolbachia endobacteria in filarial infections - exploring their usefulness as targets for novel chemotherapies that are anti-filarial and improve lymphoedema

ISRCTN	ISRCTN90861344
DOI	https://doi.org/10.1186/ISRCTN90861344
Secondary identifying numbers	1/81 306

Submission date: 19/01/2009
Registration date: 13/02/2009
Last edited: 14/08/2012

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

Institute of Medical Microbiology, Immunology and Parasitology
University of Bonn, Faculty of Medicine
Sigmund Freud Str. 25
Bonn
53105
Germany

Phone	+49 (0)228 287 15675
Email	hoerauf@microbiology-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)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study objectives	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(s)	The Committee on Human Research Publication and Ethics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana approved on 25th November 2005
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	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 study start date	01/12/2005
Completion date	30/03/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	150
Key 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
Key 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
Date of first enrolment	01/12/2005
Date of final enrolment	30/03/2009

Locations

Countries of recruitment

Germany
Ghana

Study participating centre

Institute of Medical Microbiology, Immunology and Parasitology

Bonn
53105
Germany

Sponsor information

Volkswagen Foundation (VolkswagenStiftung) (Germany)
Research organisation

c/o Dr. Detlev Hanne
Division Natural and Engineering Sciences, Medicine
Kastanienallee 35
Hannover
30519
Germany

Phone	+49 (0)511 8381 0
Email	info@volkswagenstiftung.de
Website	http://www.volkswagenstiftung.de
"ROR"	https://ror.org/03bsmfz84

Funders

Funder type

Research organisation

Volkswagen Foundation (VolkswagenStiftung) (Germany) (ref: 1/81 306)
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): VolkswagenStiftung
Location: Germany

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	01/09/2012		Yes	No