Official Title: “Effect of Albendazole Dose and Interval on Brugia Malayi Microfilarial Clearance in India: A Randomized, Open Label Study”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Dose Comparison, Parallel Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Albendazole
  • N/A
• Drug: Diethylcarbamazine
  • N/A

Primary Measures

• To determine whether increasing the albendazole dose or the frequency of treatment with DEC/albendazole is more effective than the current proved mass treatment regimen at clearing microfilaremia as assessed by microfilarial counts at 1 year.
  • Time Frame: 1 year from time enrolled.
    Safety Issue?: No

Secondary Measures

• To assess effect on adult worm burdens, microfilariae at 2 years, and Brugia specific IgG4.
  • Time Frame: 2 years from the time enrolled.
    Safety Issue?: No

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
• Hgb levels for inclusion greater than 9 g/dL
• Cr less than or equal to 1.2 mg/dL
• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Overall Contact: Thomas B. Nutman, M.D. (301) 496-5398 tnutman@niaid.nih.gov

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00511004

Study ID Number: 999907197

ClinicalTrials.gov Identifier: NCT00511004

Health Authority: United States: Federal Government