Condition category
Injury, Occupational Diseases, Poisoning
Date applied
25/07/2017
Date assigned
25/07/2017
Last edited
25/07/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Podoconiosis (endemic non-filarial elephantiasis) is a non-infectious disease that occurs in barefoot farmers who are in long-term contact with irritant red clay soil of volcanic origins. Current treatment practices of lymphedema (swelling) due to podoconiosis (PodoLE) rely on decreasing the number of acute attacks by improving the hygiene of the affected limbs. While this treatment package has been shown to be effective in halting the progression of PodoLE, it requires sustained access to resources required for limb care and strict adherence to the prescribed procedures. In two previous studies doxycycline 200mg for 6 weeks was given to patients with lymphedema due to lymphatic filariasis (LF), a parasitic disease caused by worms. This oral antibiotic treatment led to improvement or halt of the progression of the lymphedema in most of the treated patients whether their filarial infections were active or not. This led to the assumption that the same effect could also be expected in patients with PodoLE. Therefore, the aim of this study is to find out whether doxycycline (200mg/d for 6 weeks) is effective in patients with PodoLE.

Who can participate?
Patients aged 18 – 65 with a lymphedema due to podoconiosis of the leg

What does the study involve?
Participants are randomly allocated to be treated with either doxycycline 200mg or a placebo for 6 weeks. Treatments are given in addition to the standard methods of hygiene. At the start of the study and 6, 12 and 24 months later, participants undergo measurements of the leg and the skin thickness at the ankles. A questionnaire about the occurrence of acute attacks is carried out every 2 months after the start of treatment. Participants also undergo lymphedema management training at the start of the study and after 4, 6, 12, 18 and 24 months.

What are the possible benefits and risks of participating?
Benefits to the participant include thorough medical evaluation, intensified hygiene training, free supplies for local care of lymphedema and free medical treatment for common illnesses during the treatment period and follow-up. The risks to participants are side effects caused by the licensed study drug doxycycline and infection during blood sampling. In the event of side effects caused by the study drugs or treatments, participants are treated and followed up by the research team until they are resolved.

Where is the study run from?
University of Buea (Cameroon)

When is the study starting and how long is it expected to run for?
January 2017 to December 2020

Who is funding the study?
Research Networks for Health Innovations in Sub-Saharan Africa sponsored by the Federal Ministry of Education and Research (BMBF) (Germany)

Who is the main contact?
1. Prof. Samuel Wanji (public)
swanji@yahoo.fr
2. Prof. Achim Hoerauf (scientific)
achim.hoerauf@ukbonn.de

Trial website

Contact information

Type

Public

Primary contact

Prof Samuel Wanji

ORCID ID

Contact details

Public Health Parasitology and Entomology
Department of Microbiology and Parasitology
University of Buea
PO Box 63
Buea
00000
Cameroon
+237 (0)77 72 43 84
swanji@yahoo.fr

Type

Scientific

Additional contact

Prof Achim Hoerauf

ORCID ID

Contact details

Institute for Medical Microbiology
Immunology and Parasitology
University Hospital of Bonn
Sigmund-Freud-Str. 25
Bonn
53105
Germany
+49 (0)228 2871 5673
achim.hoerauf@ukbonn.de

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

TAKeOFF-5-0517

Study information

Scientific title

Doxycycline for treatment of non-filarial lymphedema due to podoconiosis (PodoLE): a randomized, placebo-controlled trial

Acronym

TAKeOFF - PodoLEDoxy

Study hypothesis

To show efficacy of a 6-week course of daily doxycycline 200 mg on lack of progression of lymphedema due to podoconiosis (PodoLE).

Ethics approval

Submission pending, documents will be submitted in September 2017 to the following boards for approval:
1. Comite Ethique de la Recherche pour la Sante Humaine (CNERSH), Yaounde, Cameroon
2. University of Buea, Faculty of Health Sciences Institutional Review Board
3. The Ethikkommission an der Medizinischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn, Bonn, Germany

Study design

Interventional randomized double-blind placebo-controlled phase II trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Home

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Podoconiosis (Podo)

Intervention

The study involves daily observed treatment with either doxycycline 200mg for 6 weeks or placebo matching doxycycline for 6 weeks (42 days). Participants with lymphedema due to pododconiosis (PodoLE) stage 2-4 will be randomized (block randomisation) to one of the two treatment regimens:
1. DOX 200: Doxycycline 200mg/d for 6 weeks (2 100mg tablets/day orally)
2. Placebo (control): Placebo matching Doxycycline for 6 weeks (2 tablets/day orally)
Treatment will be administered ad personam by the trial clinician directly in the villages in the form of daily observed treatment (DOT). All treatment regimens will be administered on top of the standardized methods of hygiene ("standard of care").Treatment will be carried out in a blinded manner, meaning that neither the patients nor the caregiver will know to which treatment arm the patients belong.

At baseline as well as 6, 12 and 24 months after treatment onset, participants will undergo lymphedema-specific measurements (circumference measurements of the leg, volume measurement of the legs, ultrasound measurement of the skin thickness at the ankles). A questionnaire regarding the occurrence of acute attacks (ADLA) will be carried out every 2 months after treatment onset. Participants will also undergo lymphedema management training at baseline and after 4, 6, 12, 18 and 24 months.

Intervention type

Drug

Phase

Phase II

Drug names

Doxycycline

Primary outcome measures

Lack of progression of lymphedema due to podoconiosis (PodoLE) (stage reduction or same stage as pre-treatment using the 5-point scale staging according to Tekola et al, 2008), examined 24 months after treatment onset

Secondary outcome measures

1. Lack of progression of PodoLE (stage reduction or same stage as pre-treatment using the 5-point scale staging according to Tekola et al, 2008), examined 6 or 12 months after treatment onset
2. Improvement of PodoLE, i.e. stage reduction (at least one stage compared to pre-treatment), examined 6, 12 and 24 months after treatment onset
3. Change of PodoLE stages (reduction or increase) compared to baseline, assessed at 6, 12 and 24 months after treatment onset
4. Changes (reduction or increase) of the circumference of the affected limbs compared to baseline circumferences, measured by tape measure at 6, 12 and 24 months after treatment onset
5. Changes of skin thickness of the affected limbs compared to baseline values, measured by ultrasound at 6, 12 and 24 months after treatment onset
6. Changes of the circumference of the affected limbs compared to baseline circumferences, measured with an infrared scanner (LymphaTech®) at 6, 12 and 24 months after treatment onset
7. Changes of the volume of the affected limbs compared to baseline volume, measured with an infrared scanner (LymphaTech®) at 6, 12 and 24 months after treatment onset
8. Changes in the duration of acute attacks compared to pre-treatment, as assessed with a questionnaire every two months after treatment onset and evaluated at 6, 12 and 24 months after treatment onset
9. Changes in the frequency of acute attacks compared to pre-treatment, as assessed with a questionnaire every two months after treatment onset and evaluated at 6, 12 and 24 months after treatment onset
10. Absence of acute attacks, as assessed with a questionnaire every two months after treatment onset and evaluated at 6, 12 and 24 months after treatment onset
11. Changes of the hygiene level compared to pre-treatment, assessed by using a hygiene survey especially developed for this study at 6, 12 and 24 months
12. Changes of the quality of life (QoL) compared to pre-treatment, assessed using the 12-item version of the WHODAS 2.0 at 12 and 24 months after treatment onset
13. Levels of angiogenic, lymphangiogenic, pro-fibrotic or pro-inflammatory biomarkers (such as VEGF, CECAM-a, MMPS) in blood and/or urine as a measure for prognostic effects, measured using ELISA and/or Luminex Multiplex Assay technique at baseline, 6, 12 and 24 months after treatment onset

Assessment of safety:
Adverse events (AE) assessed and described in the scope of the daily observed treatment (DOT). This involves:
1. Occurrence of AE
2. Intensity of AE (Grade 0 [none], Grade 1 [mild], grade 2 [moderate] grade 3 [severe])
3. SAE
4. Relation to treatment (definite, probable, possible, remote, not related)
5. Outcome of AE (restored, improved, unchanged, deteriorated, death, unknown, overcome with sequelae)
6. Intervention

Overall trial start date

01/01/2017

Overall trial end date

31/12/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Lymphedema of at least one leg grade 2-4 measured on a 5-point scale (Tekola et al, 2008)
2. Age ≥ 18 years and ≤ 65 years
3. Men or non-pregnant women. If women of childbearing-potential, they must use an approved, effective method of contraception (including abstinence) before, during and for at least 2 weeks after the completion of the active intervention with doxycycline or placebo
4. Negative pregnancy test
5. Body weight ≥ 40 kg
6. Resident in endemic area for podoconiosis for ≥ 2 years
7. Able and willing to give informed consent/ to provide assent to participate in the trial
8. Ability to use established standardized methods of hygiene and effectively applying it prior to the initiation of the drug treatment
9. Negative test for lymphatic filariasis (LF)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

N = 200

Participant exclusion criteria

1. No lymphedema, stage 1 or stage 5 lymphedema due to podoconiosis
2. Lymphedema due to lymphatic filariasis (LF)
3. Age < 18 years or > 65 years
4. Body weight < 40 kg
5. Pregnant or breastfeeding women
6. Women of childbearing potential not using an agreed method of contraception (including abstinence; oral contraceptives are not allowed because of interaction with trial drugs)
7. Clinical or biologic evidence of hepatic or renal dysfunction or disease of the central nervous system (CNS)
8. Evidence of severe comorbidities except for features of filarial disease
9. Alcohol or drug abuse
10. History of adverse reactions to doxycycline or other tetracyclines
11. Any significant condition (including medical and psychological/ psychiatric disorder) which in the opinion of the study investigator might interfere with the conduct of the study
12. History of photosensitivity reactions after taking drugs.
13. Concomitant medication with antacids containing aluminium, magnesium or sucralfate and not able to discontinue
14. Concomitant medication with other antibiotics than doxycycline and not able to discontinue
15. Concomitant medication with diuretics or sulfonylurea
16. Concomitant medication with coumarin
17. Haemoglobin < 8 gm/dL
18. Neutrophil count <2 000/mm3
19. Platelet count <100 000/mm3
20. Creatinine > 2 times upper limit of normal
21. AST (GOT) > 2 times upper limit of normal
22. ALT (GPT) > 2 times upper limit of normal
23. Gamma-GT > 2 times upper limit of normal
24. Positive urine pregnancy test
25. Positive wb123 or TBF or qPCR for W. bancrofti

Recruitment start date

01/01/2018

Recruitment end date

30/09/2018

Locations

Countries of recruitment

Cameroon

Trial participating centre

University of Buea
PO Box 63
Buea
00000
Cameroon

Sponsor information

Organisation

University of Buea

Sponsor details

PO Box 63
Buea
00000
Cameroon

Sponsor type

University/education

Website

http://www.ubuea.cm/

Funders

Funder type

Government

Funder name

Research Networks for Health Innovations in Sub-Saharan Africa sponsored by the Federal Ministry of Education and Research (BMBF), Germany

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The publication of the study results is planned in a high-impact peer reviewed journal.

IPD sharing statement
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/12/2021

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes