Will the addition of Doxycycline hyclate to standard hygiene measures be more effective compared to a placebo in improving lymphoedema grade, circumference and skin thickness in males and females aged 14 to 65 years with lymphedema caused by filarial infections?

Study Settings (Sri Lanka): Galle and Matara Districts; Snowball sampling method will be used to complete recruitment.

Study design:
This (LEDOXY-SL) trial is designed as a randomized, controlled, observer-, provider- and patient-blinded multicenter superiority trial with two parallel groups and a primary endpoint of change in grade of lymphedema at 24 months. The population will be stratified according to the Grade (Early Grade 1-3; Late Grade 4-6). Randomization will be performed as block randomization within each center in blocks of (N=4-10) for each of the groups (early and late).

Intervention
Intervention arm will receive doxycycline hyclate tablets 200mg/daily for six weeks (100mg/day for ages 14-18 years and body weight 40-50kg)

Control arm will receive identical placebo tablets 100mg – 2 tablets/day for six weeks (1 tablet/day for ages 14-18 years and body weight 40-50kg)

Standard lymphedema management protocols based on the use of simple measures of hygiene (regular washing with soap and water, skin and nail care), use of topical antibiotics or antifungal agents, exercise and footwear will be continued in both arms.

1. Age > 14 years and <65 years, male or non-pregnant women of childbearing-potential using an approved, effective method of contraception before, during and for at least 2 weeks after the completion of the active intervention with doxycycline or placebo
2. Able to give informed consent to participate in the trial
3. Resident in endemic area for five years or more
4. Body weight >40 kg
5. Lymphedema of a limb Grade 1-6 measured on a 7-point scale (Dreyer G et al. 2002).
6. Ability to use established standardized methods of hygiene and effectively applying it prior to the initiation of the drug treatment
7. No evidence of severe or systemic co-morbidities except for features of filarial disease
8. Normal laboratory profile
9. Consent to storage of blood samples for study

1. No lymphedema or lymphedema stage 7
2. Age < 14 years or > 65 years
3. Body weight < 40 kg
4. Pregnant or breastfeeding women
5. Women of childbearing potential not using an agreed method of contraception. (A pregnancy test will be conducted as part of the screening process to exclude pregnancy and repeated at 3 and 8 weeks. In addition, women of childbearing potential will be counseled against pregnancy during the treatment period)
6. Clinical or laboratory evidence of hepatic or renal dysfunction or CNS disease
7. Alcohol or drug abuse
8. History of adverse reactions to doxycycline or other tetracyclines
9. Patient has any situation or condition that may interfere with participation in the study as judged by the clinical investigator
10. Chronic headache and current headache
11. Persons who are currently taking doxycycline for other indications
12. Lymphedema due to post-radiation, post-surgical and primary (congenital) lymphedema