Clinical trial NCT00511004: Effect of Albendazole Dose on Treatment of Lymphatic Filariasis
Official title: Effect of Albendazole Dose and Interval on Brugia Malayi Microfilarial Clearance in India: A Randomized, Open Label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphatic Filariasis
Keywords: Brugia Malayi
Lymphatic Filariasis
Albendazole
Diethylcarbamazine
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2007-08-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is conducted in Kerala, India. It will determine whether a new treatment regimen of albendazole and diethylcarbamazine (DEC) for lymphatic filariasis can eliminate the disease more quickly than the standard regimen. Lymphatic filariasis is caused by infection with very small parasitic worms that are spread by mosquitoes. The disease can cause swelling of the arms, legs, breast and scrotum and can progress to permanent swelling of the legs or arms called elephantiasis. The study will see if a higher and more frequent dose of albendazole is better at clearing filarial worms from the blood than the current treatment.

Healthy people between 18 and 55 years of age who are in good health and who are infected with filarial worms may be eligible for this study.

Participants undergo the following procedures:

3-day hospital stay at the Filariasis Chemotherapy Unit of the T.D. Medical College Hospital in Kerala, India

* Random assignment to receive either: 400 mg albendazole and DEC 300 mg given once a year for 2 years (standard treatment); or 800 mg albendazole and DEC 300 mg given once a year for 2 years; or 800 mg albendazole and DEC 300 mg given twice a year for 2 years.
* Urine pregnancy test for women of childbearing age .
* Ultrasound test to look for filarial worms.
* Treatment dose.
* Monitoring for symptoms

  6-month 3-day hospital stay
* Medical history, physical examination and blood test.
* Repeat ultrasound in subjects whose first ultrasound detected adult worms.
* Treatment dose for subjects receiving medicine every 6 months.
* Urine pregnancy test for women of childbearing age.

  1-year 3-day hospital stay
* Medical history, physical examination and blood test.
* Treatment dose.
* Repeat ultrasound in subjects whose first ultrasound detected adult worms.
* Urine pregnancy test for women of childbearing age.

  18-month 3-day hospital stay
* Medical history, physical examination and blood test.
* Treatment dose for subjects receiving medicine every 6 months.
* Urine pregnancy test for women of childbearing age.

  24-month 3-day hospital stay
* Medical history, physical examination and blood test.
* Treatment dose.
* Repeat ultrasound in subjects whose first ultrasound detected adult worms.
* Urine pregnancy test for women of childbearing age.

Detailed description: Albendazole and diethylcarbamazine (DEC) are currently used in combination for annual mass treatment of lymphatic filariasis in all parts of the world except Africa. Although the drugs have been donated, the cost of such programs is very high and has proven to be a major impediment to the success of programs in many countries with limited financial resources. Data from albendazole treatment of other filarial infections and one study comparing single to multi-dose DEC/albendazole in lymphatic filariasis suggest that increased dose and/or frequency of albendazole dosing may be more effective in clearing microfilariae. In this study, 75 volunteers with microfilaremic Brugia malayi infection will be randomized to receive standard annual therapy (albendazole 400 mg + DEC 300 mg), annual therapy with increased dosing of albendazole (albendazole 800 mg + DEC 300 mg), or semiannual therapy with an increased albendazole dose (albendazole 800 mg + DEC 300 mg). Microfilarial levels will be followed every 6 months for 2 years to determine whether the higher dose, and/or the more frequent regimen, is more effective.

Eligibility criteria: * INCLUSION CRITERIA:

Inclusion Criteria for Screening:

* Age 18 years to 55 years inclusive
* Both genders
* Not pregnant or breastfeeding by history
* If selected, subjects must be willing to spend 3 days on the Filariasis Chemotherapy Unit at the T.D. Medical College Hospital, Alleppey, Kerala, India
* If selected, subjects must be willing to undergo nighttime blood draws once every 6 months and Doppler ultrasound twice yearly for 2 years
* If selected, agree to have blood stored for future studies
* Ability to understand and give informed consent

Inclusion Criteria for Treatment:

* Age 18 to 55 years inclusive
* Men and non-pregnant or non-breast feeding women
* Microfilarial levels greater than 50mf/mL
* Willingness to spend 3 days on the Filariasis Chemotherapy Unit at the T.D. Medical College Hospital, Alleppey, Kerala, India every 6 months for 2 years
* Willingness to undergo nighttime blood draws once every 6 months for 2 years
* Ability to understand and give informed consent
* Hemaglobin (Hgb) levels for inclusion greater than 9 g/dL
* Creatinine (Cr) less than or equal to 1.2 mg/dL
* Alanine aminotransferase (ALT) less than 30 U/L
* Willingness to have blood stored for future studies

EXCLUSION CRITERIA:

Exclusion Criteria for Screening:

* Age less than 18 years or greater than 55 years
* Pregnant or breast feeding by history

Exclusion Criteria for Treatment:

* Non-volunteers
* Age less than 18 years or greater than 55 years
* Pregnant or breast feeding
* Hgb levels less than or equal to 9 g/dL
* Cr greater than 1.3 mg/dL
* ALT greater than 30 U/L
* Alcohol consumption of more than 2 beers or other alcohol-containing drinks/day within a week of each drug administration
* Temperature greater than 37.5 degrees Celsius
* Serious medical illness
* History of benzimidazole allergy
* History of DEC allergy
* Use of albendazole or DEC within past 6 months
* Unwillingness to comply with required study visits

Primary outcomes:
measure: Microfilarial Counts at 1 Year
timeFrame: 1 year from time enrolled
Secondary outcomes:
measure: Adult Worm Burdens at 2 Years
timeFrame: 2 years from the time enrolled.
measure: Microfilarial Levels at 2 Years
timeFrame: 2 years from time enrolled
measure: Brugia Specific Immunoglobulin G4 (IgG4) Antibodies
timeFrame: 2 years
Other outcomes:
Locations:
city: Alleppey, Kerala
country: India
facility: Filariasis Chemotherapy Unit (FCU), T.D. Medical Hospital
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Thomas B Nutman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Edwards G, Awadzi K, Breckenridge AM, Gilles HM, Orme ML, Ward SA. Diethylcarbamazine disposition in patients with onchocerciasis. Clin Pharmacol Ther. 1981 Oct;30(4):551-7. doi: 10.1038/clpt.1981.202.
citation: Taylor HR, Greene BM. Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis. Br J Ophthalmol. 1981 Jul;65(7):494-502. doi: 10.1136/bjo.65.7.494.
citation: Partono F, Purnomo, Oemijati S, Soewarta A. The long term effects of repeated diethylcarbamazine administration with special reference to microfilaraemia and elephantiasis. Acta Trop. 1981 Sep;38(3):217-25.