Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03517462
Other study ID # 201804116
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date August 6, 2018
Est. completion date August 23, 2019

Study information

Verified date December 2020
Source Washington University School of Medicine
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The DOLF Ocular Changes after Ivermectin study will investigate the kinetics of O. volvulus microfilaria (Mf) in the eye following treatment with ivermectin. The primary objective is to determine the proportion of participants with complete Mf clearance from the eye at 3 and 6 months following treatment with ivermectin (IVM).


Description:

This study will examine the kinetics of Mf clearance in the eye following ivermectin treatment. Previous studies have been unable to fully assess clearance Mf from the posterior chamber of the eye. This study will be the first to use optical coherence tomography (OCT) in patients with onchocerciasis to document parasites and pathology in the anterior and posterior chambers of the eye, and assess ocular changes following standard ivermectin treatment. This will be a biomedical prospective cohort study. The cohort will be stratified based on Mf levels to achieve approximately the following distribution of individuals with roughly one-third of participants in each group. 1. Individuals with positive skin snip Mf density of ≥ 1 Mf/mg), but no observable Mf in eyes using slit lamp and indirect ophthalmoscopy 2. Individuals with positive skin snip Mf density of ≥ 1 Mf/mg and 1-10 Mf in either eye at baseline (based on the highest number counted in either eye) 3. Individuals with positive skin snip Mf density of ≥ 1 Mf/mg and >10 Mf in either eye at baseline. All participants recruited into the study will be treated with a single dose of ivermectin (150 ug/kg) by mouth under direct observation. This is the standard of care for treatment with onchocerciasis. Participants will be evaluated following treatment with detailed parasitological and ocular examinations 7 days, 3 months and 6 months after treatment.


Recruitment information / eligibility

Status Completed
Enrollment 231
Est. completion date August 23, 2019
Est. primary completion date August 23, 2019
Accepts healthy volunteers No
Gender All
Age group 16 Years to 70 Years
Eligibility Inclusion Criteria: - Have at least 1 palpable subcutaneous nodule (onchocercoma) and = 1 Mf/mg of skin (by skin snip) Exclusion Criteria: - Pregnancy and breastfeeding mothers within 1 month of giving birth - Have base line eye diseases including glaucoma, uveitis, severe keratitis, and/or cataracts that interfere with visualization of the posterior segment of the eye. - Prior allergic / hypersensitivity reactions or intolerance to ivermectin - Treatment with ivermectin in the past 6 (six) months

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ivermectin 3Mg Tab
ivermectin tablet

Locations

Country Name City State
Ghana University of Health and Allied Sciences Hohoe

Sponsors (3)

Lead Sponsor Collaborator
Washington University School of Medicine Case Western Reserve University, University of Health and Allied Sciences

Country where clinical trial is conducted

Ghana, 

References & Publications (42)

Anderson J, Fuglsang H. Further studies on the treatment of ocular onchocerciasis with diethylcarbamazine and suramin. Br J Ophthalmol. 1978 Jul;62(7):450-7. — View Citation

Anderson J, Fuglsang H. Ocular onchocerciasis. Trop Dis Bull. 1977 Apr;74(4):257-72. Review. — View Citation

Banla M, Tchalim S, Karabou PK, Gantin RG, Agba AI, Kére-Banla A, Helling-Giese G, Heuschkel C, Schulz-Key H, Soboslay PT. Sustainable control of onchocerciasis: ocular pathology in onchocerciasis patients treated annually with ivermectin for 23 years: a cohort study. PLoS One. 2014 Jun 2;9(6):e98411. doi: 10.1371/journal.pone.0098411. eCollection 2014. — View Citation

Basáñez MG, Pion SD, Boakes E, Filipe JA, Churcher TS, Boussinesq M. Effect of single-dose ivermectin on Onchocerca volvulus: a systematic review and meta-analysis. Lancet Infect Dis. 2008 May;8(5):310-22. doi: 10.1016/S1473-3099(08)70099-9. Review. — View Citation

Bird AC, Anderson J, Fuglsang H. Morphology of posterior segment lesions of the eye in patients with onchocerciasis. Br J Ophthalmol. 1976 Jan;60(1):2-20. — View Citation

Bird AC, el-Sheikh H, Anderson J, Fuglsang H. Changes in visual function and in the posterior segment of the eye during treatment of onchocerciasis with diethylcarbamazine citrate. Br J Ophthalmol. 1980 Mar;64(3):191-200. — View Citation

Bird AC, El-Sheikh H, Anderson J, Fuglsang H. Visual loss during oral diethylcarbamazine treatment for onchocerciasis. Lancet. 1979 Jul 7;2(8132):46. — View Citation

Braun G, McKechnie NM, Connor V, Gilbert CE, Engelbrecht F, Whitworth JA, Taylor DW. Immunological crossreactivity between a cloned antigen of Onchocerca volvulus and a component of the retinal pigment epithelium. J Exp Med. 1991 Jul 1;174(1):169-77. — View Citation

Chandrashekar R, Curtis KC, Weil GJ. Molecular characterization of a parasite antigen in sera from onchocerciasis patients that is immunologically cross-reactive with human keratin. J Infect Dis. 1995 Jun;171(6):1586-92. — View Citation

Chandrashekar R, Ogunrinade AF, Alvarez RM, Kale OO, Weil GJ. Circulating immune complex-associated parasite antigens in human onchocerciasis. J Infect Dis. 1990 Nov;162(5):1159-64. — View Citation

Dadzie KY, Bird AC, Awadzi K, Schulz-Key H, Gilles HM, Aziz MA. Ocular findings in a double-blind study of ivermectin versus diethylcarbamazine versus placebo in the treatment of onchocerciasis. Br J Ophthalmol. 1987 Feb;71(2):78-85. — View Citation

Diawara L, Traoré MO, Badji A, Bissan Y, Doumbia K, Goita SF, Konaté L, Mounkoro K, Sarr MD, Seck AF, Toé L, Tourée S, Remme JH. Feasibility of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: first evidence from studies in Mali and Senegal. PLoS Negl Trop Dis. 2009 Jul 21;3(7):e497. doi: 10.1371/journal.pntd.0000497. — View Citation

Donnelly JJ, Taylor HR, Young E, Khatami M, Lok JB, Rockey JH. Experimental ocular onchocerciasis in cynomolgus monkeys. Invest Ophthalmol Vis Sci. 1986 Apr;27(4):492-9. — View Citation

Duke BO. Human onchocerciasis--an overview of the disease. Acta Leiden. 1990;59(1-2):9-24. Review. — View Citation

Evans DS, Unnasch TR, Richards FO. Onchocerciasis and lymphatic filariasis elimination in Africa: it's about time. Lancet. 2015 May 30;385(9983):2151-2. doi: 10.1016/S0140-6736(15)61022-4. — View Citation

Fischer P, Kipp W, Bamuhiga J, Binta-Kahwa J, Kiefer A, Büttner DW. Parasitological and clinical characterization of Simulium neavei-transmitted onchocerciasis in western Uganda. Trop Med Parasitol. 1993 Dec;44(4):311-21. — View Citation

Fischer PU, King CL, Jacobson JA, Weil GJ. Potential Value of Triple Drug Therapy with Ivermectin, Diethylcarbamazine, and Albendazole (IDA) to Accelerate Elimination of Lymphatic Filariasis and Onchocerciasis in Africa. PLoS Negl Trop Dis. 2017 Jan 5;11(1):e0005163. doi: 10.1371/journal.pntd.0005163. eCollection 2017 Jan. — View Citation

Fuglsang H, Anderson J. Further observations on the relationship between ocular onchocerciasis and the head nodule, and on the possible benefit of nodulectomy. Br J Ophthalmol. 1978 Jul;62(7):445-9. — View Citation

Greene BM, Gbakima AA, Albiez EJ, Taylor HR. Humoral and cellular immune responses to Onchocerca volvulus infection in humans. Rev Infect Dis. 1985 Nov-Dec;7(6):789-95. — View Citation

Greene BM, Taylor HR, Brown EJ, Humphrey RL, Lawley TJ. Ocular and systemic complications of diethylcarbamazine therapy for onchocerciasis: association with circulating immune complexes. J Infect Dis. 1983 May;147(5):890-7. — View Citation

Greene BM, Taylor HR, Cupp EW, Murphy RP, White AT, Aziz MA, Schulz-Key H, D'Anna SA, Newland HS, Goldschmidt LP, et al. Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis. N Engl J Med. 1985 Jul 18;313(3):133-8. — View Citation

Herricks JR, Hotez PJ, Wanga V, Coffeng LE, Haagsma JA, Basáñez MG, Buckle G, Budke CM, Carabin H, Fèvre EM, Fürst T, Halasa YA, King CH, Murdoch ME, Ramaiah KD, Shepard DS, Stolk WA, Undurraga EA, Stanaway JD, Naghavi M, Murray CJL. The global burden of disease study 2013: What does it mean for the NTDs? PLoS Negl Trop Dis. 2017 Aug 3;11(8):e0005424. doi: 10.1371/journal.pntd.0005424. eCollection 2017 Aug. — View Citation

Johnson TP, Tyagi R, Lee PR, Lee MH, Johnson KR, Kowalak J, Elkahloun A, Medynets M, Hategan A, Kubofcik J, Sejvar J, Ratto J, Bunga S, Makumbi I, Aceng JR, Nutman TB, Dowell SF, Nath A. Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus. Sci Transl Med. 2017 Feb 15;9(377). pii: eaaf6953. doi: 10.1126/scitranslmed.aaf6953. — View Citation

Kamga GR, Dissak-Delon FN, Nana-Djeunga HC, Biholong BD, Mbigha-Ghogomu S, Souopgui J, Zoure HG, Boussinesq M, Kamgno J, Robert A. Still mesoendemic onchocerciasis in two Cameroonian community-directed treatment with ivermectin projects despite more than 15 years of mass treatment. Parasit Vectors. 2016 Nov 14;9(1):581. — View Citation

Kawabata M, Izui S, Anan S, Kondo S, Fukumoto S, Flores GZ, Kobayakawa T. Circulating immune complexes and their possible relevance to other immunological parameters in Guatemalan onchocerciasis. Int Arch Allergy Appl Immunol. 1983;72(2):128-33. — View Citation

Komlan K, Vossberg PS, Gantin RG, Solim T, Korbmacher F, Banla M, Padjoudoum K, Karabou P, Köhler C, Soboslay PT. Onchocerca volvulus infection and serological prevalence, ocular onchocerciasis and parasite transmission in northern and central Togo after decades of Simulium damnosum s.l. vector control and mass drug administration of ivermectin. PLoS Negl Trop Dis. 2018 Mar 1;12(3):e0006312. doi: 10.1371/journal.pntd.0006312. eCollection 2018 Mar. — View Citation

Lamberton PH, Cheke RA, Winskill P, Tirados I, Walker M, Osei-Atweneboana MY, Biritwum NK, Tetteh-Kumah A, Boakye DA, Wilson MD, Post RJ, Basañez MG. Onchocerciasis transmission in Ghana: persistence under different control strategies and the role of the simuliid vectors. PLoS Negl Trop Dis. 2015 Apr 21;9(4):e0003688. doi: 10.1371/journal.pntd.0003688. eCollection 2015 Apr. — View Citation

Opoku NO, Bakajika DK, Kanza EM, Howard H, Mambandu GL, Nyathirombo A, Nigo MM, Kasonia K, Masembe SL, Mumbere M, Kataliko K, Larbelee JP, Kpawor M, Bolay KM, Bolay F, Asare S, Attah SK, Olipoh G, Vaillant M, Halleux CM, Kuesel AC. Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial. Lancet. 2018 Oct 6;392(10154):1207-1216. doi: 10.1016/S0140-6736(17)32844-1. Epub 2018 Jan 18. Erratum in: Lancet. 2018 Oct 6;392(10154):1196. — View Citation

Progress report on the elimination of human onchocerciasis, 2015-2016. Wkly Epidemiol Rec. 2016 Oct 28;91(43):505-14. English, French. — View Citation

Rodríguez-Pérez MA, Fernández-Santos NA, Orozco-Algarra ME, Rodríguez-Atanacio JA, Domínguez-Vázquez A, Rodríguez-Morales KB, Real-Najarro O, Prado-Velasco FG, Cupp EW, Richards FO Jr, Hassan HK, González-Roldán JF, Kuri-Morales PA, Unnasch TR. Elimination of Onchocerciasis from Mexico. PLoS Negl Trop Dis. 2015 Jul 10;9(7):e0003922. doi: 10.1371/journal.pntd.0003922. eCollection 2015. — View Citation

Semba RD, Murphy RP, Newland HS, Awadzi K, Greene BM, Taylor HR. Longitudinal study of lesions of the posterior segment in onchocerciasis. Ophthalmology. 1990 Oct;97(10):1334-41. — View Citation

Taylor HR, George T. Microfilaria in the cornea in onchocerciasis. Trans R Soc Trop Med Hyg. 1987;81(1):148. — View Citation

Taylor HR, Murphy RP, Newland HS, White AT, D'Anna SA, Keyvan-Larijani E, Aziz MA, Cupp EW, Greene BM. Treatment of onchocerciasis. The ocular effects of ivermectin and diethylcarbamazine. Arch Ophthalmol. 1986 Jun;104(6):863-70. — View Citation

Taylor HR, Semba RD, Newland HS, Keyvan-Larijani E, White A, Dukuly Z, Greene BM. Ivermectin treatment of patients with severe ocular onchocerciasis. Am J Trop Med Hyg. 1989 May;40(5):494-500. — View Citation

Taylor HR. Ivermectin treatment of ocular onchocerciasis. Acta Leiden. 1990;59(1-2):201-6. Review. — View Citation

Taylor HR. Onchocerciasis. Int Ophthalmol. 1990 May;14(3):189-94. Review. — View Citation

Taylor MJ, Awadzi K, Basáñez MG, Biritwum N, Boakye D, Boatin B, Bockarie M, Churcher TS, Debrah A, Edwards G, Hoerauf A, Mand S, Matthews G, Osei-Atweneboana M, Prichard RK, Wanji S, Adjei O. Onchocerciasis Control: Vision for the Future from a Ghanian perspective. Parasit Vectors. 2009 Jan 21;2(1):7. doi: 10.1186/1756-3305-2-7. — View Citation

Thomsen EK, Sanuku N, Baea M, Satofan S, Maki E, Lombore B, Schmidt MS, Siba PM, Weil GJ, Kazura JW, Fleckenstein LL, King CL. Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis. Clin Infect Dis. 2016 Feb 1;62(3):334-341. doi: 10.1093/cid/civ882. Epub 2015 Oct 20. — View Citation

Traoré S, Wilson MD, Sima A, Barro T, Diallo A, Aké A, Coulibaly S, Cheke RA, Meyer RR, Mas J, McCall PJ, Post RJ, Zouré H, Noma M, Yaméogo L, Sékétéli AV, Amazigo UV. The elimination of the onchocerciasis vector from the island of Bioko as a result of larviciding by the WHO African Programme for Onchocerciasis Control. Acta Trop. 2009 Sep;111(3):211-8. doi: 10.1016/j.actatropica.2009.03.007. Epub 2009 Mar 31. Review. — View Citation

Wojtkowski M, Bajraszewski T, Gorczynska I, Targowski P, Kowalczyk A, Wasilewski W, Radzewicz C. Ophthalmic imaging by spectral optical coherence tomography. Am J Ophthalmol. 2004 Sep;138(3):412-9. — View Citation

Zarroug IM, Hashim K, ElMubark WA, Shumo ZA, Salih KA, ElNojomi NA, Awad HA, Aziz N, Katabarwa M, Hassan HK, Unnasch TR, Mackenzie CD, Richards F, Higazi TB. The First Confirmed Elimination of an Onchocerciasis Focus in Africa: Abu Hamed, Sudan. Am J Trop Med Hyg. 2016 Nov 2;95(5):1037-1040. Epub 2016 Jun 27. — View Citation

Zimmerman PA, Dadzie KY, De Sole G, Remme J, Alley ES, Unnasch TR. Onchocerca volvulus DNA probe classification correlates with epidemiologic patterns of blindness. J Infect Dis. 1992 May;165(5):964-8. — View Citation

* Note: There are 42 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other Assess the utility of optical coherence tomography for evaluating the presence and clearance of Mf in the anterior and posterior segments of the eye. Results from the optical coherence tomography (OCT) will be compared with slit lamp and other ocular examinations baseline, 3 and 6 months following treatment
Other Evaluate ocular changes between baseline and 3 months following ivermectin treatment using OCT Results from the optical coherence tomography (OCT) will be compared in participants pre and post treatment baseline, and 3 months following treatment
Other Evaluate ocular changes between baseline and 6 months following ivermectin treatment using OCT Results from the optical coherence tomography (OCT) will be compared in participants pre and post treatment baseline, and 6 months following treatment
Primary Number of participants with complete microfilaria clearance from the eye at 3 months Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment. Participants without Mf in the eye will be considered clear of infection in the eye. 3 months following treatment
Primary Number of participants with complete microfilaria clearance from the eye at 6 months Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment. Participants without Mf in the eye will be considered clear of infection in the eye. 6 months following treatment
Secondary The change from baseline in the number of microfilaria detected in the skin at 3 months Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. The mean skin microfilarial density will be calculated and recorded as mf/mg. baseline, and 3 months following treatment
Secondary The change from baseline in the number of microfilaria detected in the skin at 6 months Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. The mean skin microfilarial density will be calculated and recorded as mf/mg. baseline, and 6 months following treatment
Secondary The change from baseline in the number of microfilaria detected in the eye at 3 months Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment. baseline, 3 months following treatment
Secondary The change from baseline in the number of microfilaria detected in the eye at 6 months Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment. baseline, 6 months following treatment
Secondary Number of participants with complete microfilaria clearance from the skin at 3 months Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. Participants without Mf in the skin will be considered clear of infection in the skin. 3 months following treatment
Secondary Number of participants with complete microfilaria clearance from the skin at 6 months Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. Participants without Mf in the skin will be considered clear of infection in the skin. 6 months following treatment
See also
  Status Clinical Trial Phase
Completed NCT00300768 - Study Evaluating Orally Administered Moxidectin In Subjects With Onchocerca Volvulus Infection Phase 2
Not yet recruiting NCT04035174 - Evaluation of the Diagnosis Performances of DEC LTS-2 Skin Patch for Onchocerciasis in Central Africa N/A
Recruiting NCT03653975 - Clinical Features and Potential Etiology of Epilepsy and Nodding Syndrome in the Mahenge Area, Ulanga District
Completed NCT03052998 - Ivermectin Treatment in Patients With Onchocerciasis-associated Epilepsy Phase 4
Active, not recruiting NCT04311671 - Safety of a Single Dose of Moxidectin Compared With Ivermectin in Individuals Living in Onchocerciasis Endemic Areas and in Individuals Living in Onchocerciasis Endemic Areas With High Levels of Lymphatic Filariasis Co-endemicity Receiving Concomitant Albendazole Phase 3
Active, not recruiting NCT03876262 - Safety and Efficacy of Annual or Biannual Doses of Moxidectin or Ivermectin for Onchocerciasis Phase 3
Terminated NCT04913610 - Study to Assess Adverse Events, Change in Disease Activity and How Oral ABBV-4083 Capsules When Given Alone or In Combination With Albendazole Capsules Moves in The Body of Adult Participants With Onchocerca Volvulus Infection Phase 2
Completed NCT03962062 - A Pharmacokinetic and Safety Study of Moxidectin to Identify an Optimal Dose for Treatment of Children 4 to 11 Years Phase 1
Completed NCT01905436 - Mass Drug Administration for Lymphatic Filariasis and Onchocerciasis for Liberia
Recruiting NCT00001230 - Host Response to Infection and Treatment in Filarial Diseases
Completed NCT05750043 - Effect of Onchocerciasis Elimination Measures on the Incidence of Epilepsy in Maridi, South Sudan
Completed NCT05749653 - Impact of a Bi-annual CDTI on the Incidence of Epilepsy in an Onchocerciasis-endemic Area N/A
Completed NCT02078024 - Efficacy of Ivermectin and Albendazole Against Onchocerciasis in the Volta Region, Ghana Phase 3
Completed NCT00127504 - Clinical Trial of Rifampin and Azithromycin for the Treatment of River Blindness Phase 2
Completed NCT03131401 - Prevalence of LF Infection in Districts Not Included in LF Control Activities
Completed NCT02032043 - Optimization of Mass Drug Administration With Existing Drug Regimens for Lymphatic Filariasis and Onchocerciasis for Ivory Coast (DOLF-Ivory Coast)
Completed NCT04188301 - Safety and Efficacy of IDA for Onchocerciasis Phase 2
Terminated NCT05084560 - Development of AWZ1066S, a Small Molecule Anti-Wolbachia Candidate Macrofilaricide Drug Phase 1
Active, not recruiting NCT05180461 - Emodepside Phase II Trial for Treatment of Onchocerciasis Phase 2
Enrolling by invitation NCT06070116 - Safety and Efficacy of Novel Combination Regimens for Treatment of Onchocerciasis Phase 2