LoiasisPhase 4NCT01593722
Post-treatment Effects of Ivermectin (IVM) or Diethylcarbamazine (DEC) in Loiasis
A Phase 4 study testing Diethylcarbamazine and Ivermectin in people with Loiasis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cameroon.
Trial summary
Background: Loa loa is a small worm that infects people in West and Central Africa. It is spread by the bite of a fly. Adult worms live under the skin and can cause swelling in the arms, legs, and face. Some people have more serious infections in the heart, kidneys, or brain. Read more about this study
- Who is it for?
- Ages 20 to 60 years
- Conditions the study is for
- Loiasis
- What is being tested?
- Diethylcarbamazine and Ivermectin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 1 siteCameroon
- Study dates
- Apr 2012to Jan 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- A subject will be eligible for participation in the screening portion of this protocol if all of the following criteria apply:
- male or non-pregnant and not breastfeeding female subjects,
- age 20-60 years (per participant self-report)
- resident of Akonolinga
- Loa microfilaremia from 20 to 5000 mf/mL from the prior screening in the village or did not participate in the prior screening
- consent to a blood draw to screen for infection with Loa loa
Show all 10Show fewer
- must be willing to have blood samples stored
- A subject will be eligible for participation in the interventional portion of the study only if all of the following additional inclusion criteria apply:
- Loa loa microfilaremia between 20 and 2,000 mf/mL blood drawn between 11:30 am and 2:30 pm measured within 30 days prior to the baseline visit
- The subject agrees to storage of samples for study
Who cannot join
- A subject will not be eligible for participation in the screening portion of this study if any of the following conditions apply:
- Known to be pregnant (by history) or breastfeeding
- Chronic medical conditions, including but not limited to diabetes, renal or hepatic insufficiency, immunodeficiency, psychiatric disorder, seizure, that in the investigators judgments are deemed to be clinically significant
- History of hypersensitivity reaction to DEC or IVM
- A subject will not be eligible to participate in the interventional portion of the study if any of the following conditions are fulfilled at the time of enrollment:
- Pregnancy (by serum or urine beta-HCG) or breastfeeding
Show all 13Show fewer
- Chronic kidney or liver disease
- Hgb < 10 gm/dL
- Filarial infection other than Loa loa or M. perstans (O. volvulus, or W. bancrofti)
- Use of DEC or IVM within the past 6 months
- Use of immunosuppressive therapies, including steroids, within the past month
- Any condition that in the investigator s opinion places the subject at undue risk by participating in the study
- Pregnant women and children (the age of consent in Cameroon is 20 years of age) will be excluded from this study since it involves administration of medications contraindicated in pregnancy and more than minimal risk with no prospect of direct benefit, respectively.
Trial locations and contacts
1 site in 1 country.
Cameroon1 site
Filariasis and other Tropical Diseases Research Center
Yaoundé
About this study
Official title: Comparison Between the Post-Treatment Reactions After Single-dose Ivermectin or DEC in Subjects With Loa Loa Infection
Background:
- Loa loa is a small worm that infects people in West and Central Africa. It is spread by the bite of a fly. Adult worms live under the skin and can cause swelling in the arms, legs, and face. Some people have more serious infections in the heart, kidneys, or brain. Most people with Loa loa infection have no symptoms at all. The standard treatment for Loa loa infection is a medicine called diethylcarbamazine (DEC). Some people have bad reactions to DEC, including itching, muscle pains, and in severe cases coma and death.
- Another drug, ivermectin, is used in mass drug treatment programs to prevent the spread of worm infections that cause blindness and massive swelling (elephantiasis). However, people who also have Loa loa have had serious bad reactions to ivermectin. Researchers want to study both DEC and ivermectin to find out why these reactions occur. If they can be prevented, mass drug treatment programs will be able to be used in areas in Africa where Loa loa exists.
Read more
Objectives:
- To study the side effects of DEC and ivermectin treatment for Loa loa infection.
Eligibility:
- Individuals who live in 4 villages in Cameroon where Loa loa infection is known to exist, who are between 20 and 60 years of age, not pregnant or breastfeeding and have a low level of Loa loa parasites in the blood, but are otherwise healthy.
Design:
- Participants will be screened with a physical exam and medical history. Blood samples will be collected to check for Loa loa infection. Participants will also have an eye exam and provide skin samples to check for other worm infections that may interfere with the study treatment.
- Participants will be admitted to the hospital for 4 days (during and after the treatment). They will receive a single dose of either DEC or ivermectin.
- After treatment, regular blood samples will be collected. Participants will be asked questions about how they feel after treatment. Physical exams will be performed. If side effects develop, participants will be treated at the hospital.
- After leaving the hospital, participants will have followup visits. These visits will happen on days 5, 7, 9, and 14 after receiving the study medicine. They will involve a short physical exam and collection of blood samples.
- At the end of the study, participants will be offered a full 21-day DEC treatment to cure the Loa loa infection.
Read the detailed description
Ivermectin is currently used for mass drug distribution for the control of onchocerciasis and elimination of lymphatic filariasis in Africa. Due to the occurrence of severe neurologic adverse events in individuals with concomitant Loa loa infection and high levels of circulating microfilariae, drug distribution has been halted in many areas in Cameroon, Democratic Republic of Congo and other Loa-endemic countries. Diethylcarbamazine citrate (DEC) is the treatment of choice for Loa loa infection in the United States and other non-endemic countries, but can also be associated with the development of severe adverse reactions, including fatal encephalopathy, that are correlated with the number of circulating microfilariae in the blood. The cause of these reactions is unknown, and it is not known if post-treatment reactions to DEC and ivermectin both have the same underlying mechanism. Post-treatment reactions to both medications are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation. Preliminary data suggests that, unlike post-treatment responses in Wolbachia-containing filariae, inflammatory mediators commonly seen in bacterial infections and malaria, including tumor necrosis factor (TNF)-alpha and IL-1-beta, are not increased post-treatment with DEC. The aim of this study is to characterize the immunologic mechanisms of ivermectin and DEC posttreatment reactions so that it can be established whether or not these posttreatment reactions have the same underlying mechanism. An understanding of the pathophysiology of these post-treatment reactions is necessary in order to develop strategies to prevent these reactions in the future. We plan to randomize 20 subjects with low- to- moderate numbers of circulating Loa loa microfilariae to receive a single oral dose of either ivermectin (200 mcg/kg) or DEC (8 mg/kg) in an inpatient setting in Cameroon. Signs and symptoms, blood microfilarial levels, complete blood counts, intracellular and serum cytokine levels and markers of eosinophil activation will be assessed at baseline, 4 and 8 hours, and 1, 2, 3, 5, 7, and 9 and 14 days post-treatment and compared between the two treatment groups. Subjects who received ivermectin will be treated with single dose DEC (8 mg/kg) on day 14. All subjects will then be followed at 6 and 12 months post-hospitalization to determine whether they have experienced Loa-specific symptoms (eyeworm or Calabar swellings). Mf count and complete blood count (CBC) with differential will be obtained at each follow-up visit. Subjects with Loa-specific symptoms or mf counts > 100 mf/mL at the 6 month time point will be offered a full treatment course. If > 50% of subjects meet criteria for full DEC treatment at the 6, month time point, all subjects will be treated and the study will enter a follow-up phase with a visit at 12 months (6 months after the full treatment course ).
- Conditions
- Loiasis
- Being tested
- Diethylcarbamazine, Ivermectin
- Keywords
- Loa loa, Immune Response, Therapy
- Medical subject headings
- Loiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiethylcarbamazineDrug
Also called Hetrazan, Banocide
single dose
IvermectinDrug
Also called Mectizan, Stromectol
single dose
| Study group | Role | What they receive |
|---|---|---|
| diethylcarbamazine | Active comparator | diethylcarbamazine 8 mg/kg single oral dose Receives: Drug: Diethylcarbamazine |
| ivermectin | Active comparator | ivermectin 200 mcg/kg single oral dose Receives: Drug: Ivermectin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Peak % of Baseline Eosinophil Count Measured During the First 7 Days Post-treatment.
Measured: 7 days
Secondary outcomes (3)
The Frequency of Adverse Events
Symptoms, signs and laboratory abnormalities occurring in the 7 days post-treatment
Measured: 7 days
Eosinophil Activation
Levels of surface marker expression on eosinophils
Measured: 3 days
Proportion of Subjects Who Clear Microfilaremia
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2012 (estimated)
- Study startApr 2012
- Primary completionAug 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for LoiasisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Amy D Klion, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01593722
- Sponsor's protocol ID
- 999912117
- Other IDs
- 12-I-N117
- Status last verified
- Sep 2016
- First submitted
- 5 May 2012
- Last updated
- 9 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Klion AD, Massougbodji A, Sadeler BC, Ottesen EA, Nutman TB. Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. J Infect Dis. 1991 Jun;163(6):1318-25. doi: 10.1093/infdis/163.6.1318.
PubMed 2037798Boussinesq M. Loiasis. Ann Trop Med Parasitol. 2006 Dec;100(8):715-31. doi: 10.1179/136485906X112194.
PubMed 17227650Winkler S, Paiha S, Winkler H, Graninger W, Marberger M, Steiner GE. Microfilarial clearance in loiasis involves elevation of Th1 and Th2 products and emergence of a specific pattern of T-cell populations. Parasite Immunol. 1996 Sep;18(9):479-82. doi: 10.1111/j.1365-3024.1996.tb01032.x.
PubMed 9226684Herrick JA, Legrand F, Gounoue R, Nchinda G, Montavon C, Bopda J, Tchana SM, Ondigui BE, Nguluwe K, Fay MP, Makiya M, Metenou S, Nutman TB, Kamgno J, Klion AD. Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection. Clin Infect Dis. 2017 Apr 15;64(8):1017-1025. doi: 10.1093/cid/cix016.
PubMed 28329346
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison Between the Post-Treatment Reactions After Single-dose Ivermectin or DEC in Subjects With Loa Loa Infection
- ClinicalTrials.gov ID
- NCT01593722
- Acronym / sponsor ID
- 999912117
- Conditions
- Loiasis
- Keywords
- Loa loa, Immune Response, Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 155 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Apr 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 8 May 2012 (estimated)
- Results
- Posted 9 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Loa loa is a small worm that infects people in West and Central Africa. It is spread by the bite of a fly. Adult worms live under the skin and can cause swelling in the arms, legs, and face. Some people have more serious infections in the heart, kidneys, or brain. Most people with Loa loa infection have no symptoms at all. The standard treatment for Loa loa infection is a medicine called diethylcarbamazine (DEC). Some people have bad reactions to DEC, including itching, muscle pains, and in severe cases coma and death.
- Another drug, ivermectin, is used in mass drug treatment programs to prevent the spread of worm infections that cause blindness and massive swelling (elephantiasis). However, people who also have Loa loa have had serious bad reactions to ivermectin. Researchers want to study both DEC and ivermectin to find out why these reactions occur. If they can be prevented, mass drug treatment programs will be able to be used in areas in Africa where Loa loa exists.
Objectives:
- To study the side effects of DEC and ivermectin treatment for Loa loa infection.
Eligibility:
- Individuals who live in 4 villages in Cameroon where Loa loa infection is known to exist, who are between 20 and 60 years of age, not pregnant or breastfeeding and have a low level of Loa loa parasites in the blood, but are otherwise healthy.
Design:
- Participants will be screened with a physical exam and medical history. Blood samples will be collected to check for Loa loa infection. Participants will also have an eye exam and provide skin samples to check for other worm infections that may interfere with the study treatment.
- Participants will be admitted to the hospital for 4 days (during and after the treatment). They will receive a single dose of either DEC or ivermectin.
- After treatment, regular blood samples will be collected. Participants will be asked questions about how they feel after treatment. Physical exams will be performed. If side effects develop, participants will be treated at the hospital.
- After leaving the hospital, participants will have followup visits. These visits will happen on days 5, 7, 9, and 14 after receiving the study medicine. They will involve a short physical exam and collection of blood samples.
- At the end of the study, participants will be offered a full 21-day DEC treatment to cure the Loa loa infection.
Detailed description
Ivermectin is currently used for mass drug distribution for the control of onchocerciasis and elimination of lymphatic filariasis in Africa. Due to the occurrence of severe neurologic adverse events in individuals with concomitant Loa loa infection and high levels of circulating microfilariae, drug distribution has been halted in many areas in Cameroon, Democratic Republic of Congo and other Loa-endemic countries. Diethylcarbamazine citrate (DEC) is the treatment of choice for Loa loa infection in the United States and other non-endemic countries, but can also be associated with the development of severe adverse reactions, including fatal encephalopathy, that are correlated with the number of circulating microfilariae in the blood. The cause of these reactions is unknown, and it is not known if post-treatment reactions to DEC and ivermectin both have the same underlying mechanism. Post-treatment reactions to both medications are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation. Preliminary data suggests that, unlike post-treatment responses in Wolbachia-containing filariae, inflammatory mediators commonly seen in bacterial infections and malaria, including tumor necrosis factor (TNF)-alpha and IL-1-beta, are not increased post-treatment with DEC. The aim of this study is to characterize the immunologic mechanisms of ivermectin and DEC posttreatment reactions so that it can be established whether or not these posttreatment reactions have the same underlying mechanism. An understanding of the pathophysiology of these post-treatment reactions is necessary in order to develop strategies to prevent these reactions in the future. We plan to randomize 20 subjects with low- to- moderate numbers of circulating Loa loa microfilariae to receive a single oral dose of either ivermectin (200 mcg/kg) or DEC (8 mg/kg) in an inpatient setting in Cameroon. Signs and symptoms, blood microfilarial levels, complete blood counts, intracellular and serum cytokine levels and markers of eosinophil activation will be assessed at baseline, 4 and 8 hours, and 1, 2, 3, 5, 7, and 9 and 14 days post-treatment and compared between the two treatment groups. Subjects who received ivermectin will be treated with single dose DEC (8 mg/kg) on day 14. All subjects will then be followed at 6 and 12 months post-hospitalization to determine whether they have experienced Loa-specific symptoms (eyeworm or Calabar swellings). Mf count and complete blood count (CBC) with differential will be obtained at each follow-up visit. Subjects with Loa-specific symptoms or mf counts > 100 mf/mL at the 6 month time point will be offered a full treatment course. If > 50% of subjects meet criteria for full DEC treatment at the 6, month time point, all subjects will be treated and the study will enter a follow-up phase with a visit at 12 months (6 months after the full treatment course ).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| diethylcarbamazine | Active comparator | Drug: Diethylcarbamazinediethylcarbamazine 8 mg/kg single oral dose |
| ivermectin | Active comparator | Drug: Ivermectinivermectin 200 mcg/kg single oral dose |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- A subject will be eligible for participation in the screening portion of this protocol if all of the following criteria apply:
- male or non-pregnant and not breastfeeding female subjects,
- age 20-60 years (per participant self-report)
- resident of Akonolinga
- Loa microfilaremia from 20 to 5000 mf/mL from the prior screening in the village or did not participate in the prior screening
Key exclusion criteria (13 listed)
- A subject will not be eligible for participation in the screening portion of this study if any of the following conditions apply:
- Known to be pregnant (by history) or breastfeeding
- Chronic medical conditions, including but not limited to diabetes, renal or hepatic insufficiency, immunodeficiency, psychiatric disorder, seizure, that in the investigators judgments are deemed to be clinically significant
- History of hypersensitivity reaction to DEC or IVM
- A subject will not be eligible to participate in the interventional portion of the study if any of the following conditions are fulfilled at the time of enrollment:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiethylcarbamazineAlso: Hetrazan, Banocidesingle dose | Drug | diethylcarbamazine |
| IvermectinAlso: Mectizan, Stromectolsingle dose | Drug | ivermectin |
Primary outcome
The Peak % of Baseline Eosinophil Count Measured During the First 7 Days Post-treatment.
Time frame: 7 days
3 secondary outcomes
The Frequency of Adverse Events
Time frame: 7 days
Eosinophil Activation
Time frame: 3 days
Proportion of Subjects Who Clear Microfilaremia
Time frame: 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2037798Klion AD, Massougbodji A, Sadeler BC, Ottesen EA, Nutman TB. Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. J Infect Dis. 1991 Jun;163(6):1318-25. doi: 10.1093/infdis/163.6.1318.
- Background: PubMed 17227650Boussinesq M. Loiasis. Ann Trop Med Parasitol. 2006 Dec;100(8):715-31. doi: 10.1179/136485906X112194.
- Background: PubMed 9226684Winkler S, Paiha S, Winkler H, Graninger W, Marberger M, Steiner GE. Microfilarial clearance in loiasis involves elevation of Th1 and Th2 products and emergence of a specific pattern of T-cell populations. Parasite Immunol. 1996 Sep;18(9):479-82. doi: 10.1111/j.1365-3024.1996.tb01032.x.
- Derived from this study: PubMed 28329346Herrick JA, Legrand F, Gounoue R, Nchinda G, Montavon C, Bopda J, Tchana SM, Ondigui BE, Nguluwe K, Fay MP, Makiya M, Metenou S, Nutman TB, Kamgno J, Klion AD. Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection. Clin Infect Dis. 2017 Apr 15;64(8):1017-1025. doi: 10.1093/cid/cix016.
Related trials for Loiasis
Not yet recruitingPhase 3
21-day Double-blind Trial of Albendazole in Adults With Loa Loa Microfilaremia
Loiasis With Positive Blood Microfilaremia, Loiasis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy D Klion, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Diethylcarbamazine and Ivermectin in people with Loiasis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cameroon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cameroon. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Peak % of Baseline Eosinophil Count Measured During the First 7 Days Post-treatment. (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01593722, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2016.