Doxycycline to Treat Mansonella Perstans Infection in Patients With and Without Lymphatic Filariasis
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Mansonella Perstans Infection; Mp Microfilaremia
Intervention: Doxycycline (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Summary
This study will examine: 1) the safety and effectiveness of the drug doxycycline in reducing
the number of Mansonella perstans (Mp) worms in the blood of infected patients, and 2) the
effects of doxycycline followed by albendazole and ivermectin treatment for lymphatic
filariasis, caused by the parasitic worm Wuchereria bancofti (Wb).
Both Mp and Wb very small filarial worms that are spread by mosquitoes. Some people are
infected with both Mp and Wb. Although most people do not become ill from infection with
these parasites, some develop symptoms. Wb can cause swellings in the arms, legs, breast,
and scrotum, and can progress to permanent swelling of the legs or arms called
elephantiasis. Mp can cause itching, swelling, fever, headache, or other symptoms.
Ivermectin and albendazole are medicines used to treat lymphatic filariasis. They eliminate
the Wb parasite from the blood but do not affect Mp. Doxycycline is used to treat many kinds
of infections and has also recently been shown to reduce the number of filarial worms in
several types of filarial infections. The drug may be useful in Mp infections as well.
Residents of Sabougou and nearby villages in Mali who are infected with the Mp parasite, are
between 14 and 65 years of age, are in good health, are not pregnant or breastfeeding, and
weigh at least 40 kg (88 lb) may be eligible for this study. They may or may not also be
infected with Wb. Candidates are screened with a brief medical history and physical
examination and blood tests to look for infection with Mp and Wb.
Participants undergo a complete physical examination and medical history. Blood is drawn for
routine blood tests. Participants are then randomly assigned to one of four treatment
groups, as follows: 1) doxycycline for 6 weeks; 2) doxycycline for 6 weeks followed by a
single dose of albendazole and ivermectin given 6 months after the beginning of doxycycline
treatment; 3) a single dose of albendazole and ivermectin given 6 months after the beginning
of doxycycline treatment; or 4) no treatment. Only patients infected with Wb receive
albendazole and ivermectin treatment.
All participants, whether or not they receive doxycycline, come to the clinic every day for
6 weeks. Every 2 weeks during this time, they have a blood test and, in women of
childbearing age, a urine pregnancy test. After 6 months, they have a medical history,
physical examination, and blood tests. Subjects in the albendazole/ivermectin treatment
group are given the pills to take at that time. One year and three years after beginning the
study, participants return to the clinic for a final history, physical examination, and
blood tests.
At the end of the first year of the study, all participants who tested positive for
lymphatic filariasis but did not receive ivermectin and albendazole will be offered
treatment with these medicines Ivermectin and albendazole will also be distributed by the
Mali government to everyone in the villages as part of a program to eliminate lymphatic
filariasis in the country.
Clinical Details
Official title: Treatment of Mansonella Perstans Infection in an Area Coendemic for Lymphatic Filariasis: A Pilot Study of the Effects of Doxycycline
Study design: Primary Purpose: Treatment
Primary outcome: Greater than or equal to 50 percent of Mp microfilaremia at 1 year in response to doxycycline treatment in study volunteers with Mp infection.
Detailed description:
Mansonella perstans (Mp) infection is common in areas of Africa that are endemic for
Wuchereria bancrofti (Wb), a causative agent of lymphatic filariasis. The clinical and
immunologic contributions of Mp infection in this setting are unknown, in part because of
the lack of response of Mp to standard antifilarial therapies. The recent discovery of
bacterial endosymbionts (Wolbachia) in a number of filarial species, including Mp, has led
to new therapeutic options for reducing microfilaremia. Volunteers between the ages of 14
and 65 will be screened in order to identify 240 volunteers (160 Wb+Mp+ and 80 Wb-Mp+) for
participation in an open label randomized trial of doxycycline (200 mg daily for 6 weeks).
Wb+Mp+ subjects will then be randomized to receive single dose treatment with albendazole
and ivermectin 4 months after completion of the doxycycline treatment or no further
treatment. Clinical, parasitologic and immunologic assessments will be performed prior to
the initiation of treatment and at 6 months and 1 year and 3 years following initiation of
treatment. The efficacy of doxycycline treatment in reducing Mp microfilaremia will be
assessed in subjects with and without Wb coinfection. In addition, the effect of subsequent
administration of albendazole/ivermectin on Mp clearance will be assessed in coinfected
subjects.
Eligibility
Minimum age: 14 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA - SCREENING:
Age 14 to 65.
Both genders.
Not pregnant or breastfeeding by history.
EXCLUSION CRITERIA - SCREENING:
Non-volunteers.
Age less than 14 or greater than 65.
Pregnant or breastfeeding by history.
INCLUSION CRITERIA - TREATMENT:
Age 14 to 65 years.
Men and non-pregnant or breastfeeding women.
EXCLUSION CRITERIA - TREATMENT:
Non-volunteers.
Age less than 14 or greater than 65.
Pregnancy or breast-feeding.
Hgb less than or equal to 10 g/dl.
Cr greater than 1. 4/100 ml.
ALT greater than 45 U or bilirubin greater than 1. 5.
Weight less than 40 kg.
Heavy alcohol use (more than 1 beer or other alcohol-containing drink/day).
Temperature greater than 37. 5C or other serious medical illnesses.
History of allergy to doxycycline or other tetracyclines.
History of HIV infection or other immunocompromised state.
Locations and Contacts
National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pi, Bethesda, Maryland 20892, United States
Additional Information
Related publications: Beach MJ, Streit TG, Addiss DG, Prospere R, Roberts JM, Lammie PJ. Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren. Am J Trop Med Hyg. 1999 Mar;60(3):479-86. Addiss DG, Beach MJ, Streit TG, Lutwick S, LeConte FH, Lafontant JG, Hightower AW, Lammie PJ. Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children. Lancet. 1997 Aug 16;350(9076):480-4. Erratum in: Lancet 1997 Oct 4;350(9083):1036. Horton J, Witt C, Ottesen EA, Lazdins JK, Addiss DG, Awadzi K, Beach MJ, Belizario VY, Dunyo SK, Espinel M, Gyapong JO, Hossain M, Ismail MM, Jayakody RL, Lammie PJ, Makunde W, Richard-Lenoble D, Selve B, Shenoy RK, Simonsen PE, Wamae CN, Weerasooriya MV. An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis. Parasitology. 2000;121 Suppl:S147-60. Review.
Starting date: December 2004
Last updated: June 1, 2012
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