Lymphatic Filariasis Clinical Trial
Official title:
Alternative Chemotherapies for Lymphatic Filariasis (LF) Treatment and Elimination in Africa [Cote d'Ivoire]
Verified date | April 2019 |
Source | University Hospitals Cleveland Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The recommended treatment for elimination of LF in sub-Saharan Africa is annual mass drug administration (MDA) with single dose Albendazole (ALB) plus Ivermectin (IVM) given for at least 5-7 years. However, in areas where LF is co-endemic with a related filarial parasite, Loa loa, co-infection with L. loa represents a serious barrier to LF elimination because IVM used in LF MDA can result in severe reactions and even death in individuals with high microfilaria (mf) levels of L. loa. Screening for heavy L. loa infection is problematic. To overcome this problem, monotherapy with ALB is possible, since this drug has little or no effect on circulating mf and thus would not cause adverse effects in people with heavy L. loa infections. Moreover ALB has been shown to have embryostatic or embryocidal effects in female adult worms resulting in decreased mf levels with time as natural attrition of circulating mf occurs. Thus this open-label, randomized clinical trial will examine treatment with ALB monotherapy administered twice per year over a period of 3 years with the primary endpoint being the proportion of individuals with total clearance of mf at 36 months and Alere antigen test negativity (a more sensitive circulating antigen test of filarial infection). Two of the treatment arms will include ALB at two different doses, 400mg or 800mg (fixed dose twice yearly) as compared to standard treatment of ALB (400 mg) plus IVM (150-200 µg/kg) administered annually. Observations from an ongoing clinical trial in Papua New Guinea suggest that a single dose of triple therapy with ALB + IVM + DEC may be highly effective in sterilizing adult female worms. Therefore to confirm and expand these important preliminary observations in a different population, a fourth arm will be included in the current clinical trial in which subjects will receive all three drugs. The clinical trial will be performed in a region of Cote d'Ivoire where onchocerciasis and loiasis are not endemic.
Status | Completed |
Enrollment | 189 |
Est. completion date | September 25, 2018 |
Est. primary completion date | September 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: - Women and men 18-70 years - =50 MF/mL based on Nuclepore filtration - Willing to give informed consent Exclusion Criteria: - Prior treatment for LF within last 5 years - Pregnancy (perform pregnancy test) - Hemoglobin <7 g/dL - Permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension - AST/ALT and creatinine >1.5 upper limit of normal - Proteinuria or hematuria >3+ - Skin snip positivity for O. volvulus MF |
Country | Name | City | State |
---|---|---|---|
Côte D'Ivoire | Cote d'Ivoire | Abidjan |
Lead Sponsor | Collaborator |
---|---|
University Hospitals Cleveland Medical Center | Washington University School of Medicine |
Côte D'Ivoire,
Awadzi K, Edwards G, Duke BO, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quartey BT. The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2003 Mar;97(2):165-78. — View Citation
Awadzi K, Edwards G, Opoku NO, Ardrey AE, Favager S, Addy ET, Attah SK, Yamuah LK, Quartey BT. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2004 Sep;98(6):595-614. — View Citation
Bockarie MJ, Tavul L, Ibam I, Kastens W, Hazlett F, Tisch DJ, Alpers MP, Kazura JW. Efficacy of single-dose diethylcarbamazine compared with diethylcarbamazine combined with albendazole against Wuchereria bancrofti infection in Papua New Guinea. Am J Trop Med Hyg. 2007 Jan;76(1):62-6. — View Citation
Boussinesq M, Kamgno J, Pion SD, Gardon J. What are the mechanisms associated with post-ivermectin serious adverse events? Trends Parasitol. 2006 Jun;22(6):244-6. Epub 2006 Apr 24. — View Citation
Chu, B. K., P. J. Hooper, M. H. Bradley, D. A. McFarland and E. A. Ottesen
Geary TG, Mackenzie CD. Progress and challenges in the discovery of macrofilaricidal drugs. Expert Rev Anti Infect Ther. 2011 Aug;9(8):681-95. doi: 10.1586/eri.11.76. Review. — View Citation
Geary TG. Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol. 2005 Nov;21(11):530-2. Epub 2005 Aug 26. Review. — View Citation
Hoerauf A, Pfarr K, Mand S, Debrah AY, Specht S. Filariasis in Africa--treatment challenges and prospects. Clin Microbiol Infect. 2011 Jul;17(7):977-85. doi: 10.1111/j.1469-0691.2011.03586.x. Review. — View Citation
Hooper PJ, Bradley MH, Biswas G, Ottesen EA. The Global Programme to Eliminate Lymphatic Filariasis: health impact during its first 8 years (2000-2007). Ann Trop Med Parasitol. 2009 Oct;103 Suppl 1:S17-21. doi: 10.1179/000349809X12502035776513. — View Citation
Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002 Dec;15(6):599-608. Review. — View Citation
Horton J. The development of albendazole for lymphatic filariasis. Ann Trop Med Parasitol. 2009 Oct;103 Suppl 1:S33-40. doi: 10.1179/000349809X12502035776595. Review. — View Citation
Hotez PJ, Savioli L, Fenwick A. Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control. PLoS Negl Trop Dis. 2012;6(2):e1475. doi: 10.1371/journal.pntd.0001475. Epub 2012 Feb 28. Review. — View Citation
Kitzman D, Wei SY, Fleckenstein L. Liquid chromatographic assay of ivermectin in human plasma for application to clinical pharmacokinetic studies. J Pharm Biomed Anal. 2006 Mar 3;40(4):1013-20. Epub 2005 Oct 19. — View Citation
Mand S, Debrah A, Batsa L, Adjei O, Hoerauf A. Reliable and frequent detection of adult Wuchereria bancrofti in Ghanaian women by ultrasonography. Trop Med Int Health. 2004 Oct;9(10):1111-4. — View Citation
McGarry HF, Plant LD, Taylor MJ. Diethylcarbamazine activity against Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway. Filaria J. 2005 Jun 2;4:4. — View Citation
Moreno Y, Nabhan JF, Solomon J, Mackenzie CD, Geary TG. Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20120-5. doi: 10.1073/pnas.1011983107. Epub 2010 Nov 1. — View Citation
Ottesen EA, Duke BO, Karam M, Behbehani K. Strategies and tools for the control/elimination of lymphatic filariasis. Bull World Health Organ. 1997;75(6):491-503. Review. — View Citation
Ottesen EA, Hooper PJ, Bradley M, Biswas G. The global programme to eliminate lymphatic filariasis: health impact after 8 years. PLoS Negl Trop Dis. 2008 Oct 8;2(10):e317. doi: 10.1371/journal.pntd.0000317. — View Citation
Ottesen EA. Lymphatic filariasis: Treatment, control and elimination. Adv Parasitol. 2006;61:395-441. Review. — View Citation
Teruel M, Dercole J, Catalano R. Evaluation of potential embryo toxicity of albendazole sulphoxide in CF1 mice. Biocell. 2011 Apr;35(1):29-33. — View Citation
Weil GJ, Curtis KC, Fakoli L, Fischer K, Gankpala L, Lammie PJ, Majewski AC, Pelletreau S, Won KY, Bolay FK, Fischer PU. Laboratory and field evaluation of a new rapid test for detecting Wuchereria bancrofti antigen in human blood. Am J Trop Med Hyg. 2013 Jul;89(1):11-15. doi: 10.4269/ajtmh.13-0089. Epub 2013 May 20. — View Citation
Zouré HG, Wanji S, Noma M, Amazigo UV, Diggle PJ, Tekle AH, Remme JH. The geographic distribution of Loa loa in Africa: results of large-scale implementation of the Rapid Assessment Procedure for Loiasis (RAPLOA). PLoS Negl Trop Dis. 2011 Jun;5(6):e1210. doi: 10.1371/journal.pntd.0001210. Epub 2011 Jun 28. — View Citation
* Note: There are 22 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Total clearance of Microfilariae | The percentage of participants with total clearance of Microfilariae | 36 months | |
Secondary | Total clearance of MF at 24 months | Percentage of subjects with total clearance of MF at 24 months | 24 months | |
Secondary | Percent MF reduction | Percent MF reduction at 24 and 36 months compared to baseline level | 24 and 36 months | |
Secondary | Reduction in W. bancrofti antigen level | Percent reduction in W. bancrofti antigen level measured by Og4C3 assay at 12, 24 and 36 months compared to baseline level | 12, 24 and 36 months | |
Secondary | Alere Filariasis Test Strip negative | Percentage of subjects that become Alere Filariasis Test Strip negative at 12, 24 and 36 months | 12, 24 and 36 months | |
Secondary | reduction in viable worm nests | Percent reduction in viable worm nests relative to baseline (time 0) based on follow up scrotal ultrasound examination performed at 12, 24 and 36 months | 12, 24, and 36 months | |
Secondary | Diversity of parasites | Diversity of parasites before and after treatment using genetic markers | 0 and 36 months | |
Secondary | type and level of parasite-specific host immune response | Relation of type and level of parasite-specific host immune response with the initial and sustained clearance of parasites | 0 and 36 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT00375583 -
Effect of Albendazole Dose on Clearance of Filarial Worms
|
Phase 2 | |
Completed |
NCT03664063 -
PK PD Study of IDA and Azithromycin for NTDs ( ComboNTDs )
|
Phase 2 | |
Recruiting |
NCT04844905 -
Adjunctive Ivermectin Mass Drug Administration for Malaria Control
|
Phase 3 | |
Completed |
NCT01975441 -
Eval 3-Drug Therapy Diethylcarbamize, Albendazole and Ivermectin That Could Accelerate LF Elimination Outside of Africa
|
Phase 2 | |
Completed |
NCT01629771 -
Disability and Quality of Life in Patients With Lymphatic Filariasis in Rural Southern India
|
N/A | |
Completed |
NCT01905423 -
Optimization of Mass Drug Administration With Existing Drug Regimens for Lymphatic Filariasis and Onchocerciasis
|
||
Completed |
NCT02784743 -
Impact of Albendazole -Ivermectin on Wuchereria Bancrofti in Mali
|
Phase 4 | |
Completed |
NCT03036059 -
Twice Yearly Treatment for the Control of LF
|
Phase 4 | |
Completed |
NCT01905436 -
Mass Drug Administration for Lymphatic Filariasis and Onchocerciasis for Liberia
|
||
Completed |
NCT02509481 -
Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study
|
Phase 2/Phase 3 | |
Completed |
NCT03268252 -
Optimization of MDA With Existing Drug Regimens for LF: Monitoring Efficacy of Ongoing Treatment Programs in PNG
|
||
Completed |
NCT02927496 -
A 24 Month Study, to Compare the Efficacy of Doxycycline vs. Placebo for Improving Filarial Lymphedema in Mali
|
Phase 3 | |
Completed |
NCT02899936 -
Death to Onchocerciasis and Lymphatic Filariasis (DOLF) Triple Drug Therapy for Lymphatic Filariasis
|
N/A | |
Completed |
NCT00511004 -
Effect of Albendazole Dose on Treatment of Lymphatic Filariasis
|
Phase 2 | |
Active, not recruiting |
NCT04258670 -
Spontaneous Antigenemia in Loiasis
|
||
Terminated |
NCT01213576 -
Efficacy of Higher Albendazole and Ivermectin Doses on Wuchereria Bancrofti Microfilarial Clearance in Malawi
|
N/A | |
Completed |
NCT02929121 -
A 24 Month Study to Compare Efficacy of Doxycycline vs Placebo for Improving Filarial Lymphedema in India
|
Phase 3 | |
Completed |
NCT00339417 -
Effect of Albendazole Dose on Clearance of Filarial Worms
|
Phase 2 | |
Completed |
NCT02032043 -
Optimization of Mass Drug Administration With Existing Drug Regimens for Lymphatic Filariasis and Onchocerciasis for Ivory Coast (DOLF-Ivory Coast)
|
||
Withdrawn |
NCT01903057 -
Safety Study of Combined Azithromycin, Ivermectin and Albendazole for Trachoma and Lymphatic Filariasis
|
Phase 4 |