Doxycycline to Treat Mansonella Perstans Infection in Patients With and Without Lymphatic Filariasis - Full Text View

Purpose

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.

Condition	Intervention	Phase
Mansonella Perstans Infection Mp Microfilaremia	Drug: Doxycycline	Phase 2


Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	Treatment of Mansonella Perstans Infection in an Area Coendemic for Lymphatic Filariasis: A Pilot Study of the Effects of Doxycycline

Resource links provided by NLM:

Genetics Home Reference related topics: lymphedema-distichiasis syndrome

Drug Information available for: Doxycycline Doxycycline monohydrate Doxycycline hyclate Doxycycline calcium

Genetic and Rare Diseases Information Center resources: Acanthocheilonemiasis Helminthiasis Lymphatic Filariasis Mansonelliasis

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Greater than or equal to 50 percent of Mp microfilaremia at 1 year in response to doxycycline treatment in study volunteers with Mp infection. [ Designated as safety issue: Yes ]


Estimated Enrollment:	1500
Study Start Date:	December 2004
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

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


Ages Eligible for Study:	14 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00340691

Locations


United States, Maryland
National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pi
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

More Information

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Coulibaly YI, Dembele B, Diallo AA, Lipner EM, Doumbia SS, Coulibaly SY, Konate S, Diallo DA, Yalcouye D, Kubofcik J, Doumbo OK, Traore AK, Keita AD, Fay MP, Traore SF, Nutman TB, Klion AD. A randomized trial of doxycycline for Mansonella perstans infection. N Engl J Med. 2009 Oct 8;361(15):1448-58. doi: 10.1056/NEJMoa0900863.


Responsible Party:	Amy Klion, M.D./National Institute of Allergy and Infectious Diseases, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00340691 History of Changes
Other Study ID Numbers:	999905053, 05-I-N053
Study First Received:	June 19, 2006
Last Updated:	June 1, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):


Parasite Chemotherapy Wuchereria Bancrofti

Additional relevant MeSH terms:


Acanthocheilonemiasis Dipetalonema Infections Elephantiasis Elephantiasis, Filarial Filariasis Mansonelliasis Helminthiasis Lymphatic Diseases Lymphedema Nematode Infections Parasitic Diseases	Secernentea Infections Spirurida Infections Doxycycline Anti-Bacterial Agents Anti-Infective Agents Antimalarials Antiparasitic Agents Antiprotozoal Agents Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015