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We hypothesize that ivermectin, a drug used to treat parasitic worm infections, interacts with the human innate immune system and that this contributes to its anti-parasitic effects. Participants will donate blood before and after being administered the normal human dose of the drug. We will compare the cell types present in the blood and the chemicals known to influence the human immune system before and after the drug is given, as well as measuring any changes in gene expression in white blood cells 4 and 24hrs after the drug is taken.
Subjects will visit the University of Georgia (UGA) Clinical & Translation Research Unit (CTRU) twice on consecutive days and blood will be drawn from them. On the first occasion they will be weighed and will complete the consent process. They will have been randomly assigned to the test (Stromectol) or control (placebo) group, with 8 participants in the test group and 4 participants in the control group. Stromectol will be obtained from a medical supply distributor and a placebo will be obtained through the UGA School of Pharmacy. Drugs will be prescribed by Jonathan Murrow MD. They will be stored in their original packaging at room temperature in a drug locker in the lab at CTRU. Participants will be identified by number and allocated to groups using a block randomization protocol. Randomization and drug dispensation will be done by CTRU. Eighteen ml of blood will drawn in a fasting state and they will be administered 150 mcg/kg Stromectol or the equivalent number of placebo tablets immediately after blood is drawn. Participants will remain at CTRU for four hours after they take the drug, then another 15ml of blood will be drawn. On the second day they will attend CTRU at the same time and the third blood sample will be drawn 24 hrs after administration of the drug. On each occasion the drawn blood will be coded by CTRU staff prior to being collected by a member of the Department of Infectious Diseases and taken to the laboratory (Wildlife Health G0007) for the isolation of leukocyte populations (peripheral monocytes, lymphocytes and polymorphonuclear cells (PMNs)) and for the preparation of serum. Complete blood counts will also be carried out. Sera will be analyzed on the Luminex for cytokine/chemokine content. RNA will be isolated from the cell populations for RNASeq analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ivermectin | Active Comparator | Ivermectin will be administered once at 150mcg/kg, orally. |
|
| Control | Placebo Comparator | An oral placebo will be administered once |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivermectin | Drug | 150 mcg/kg ivermectin, by mouth. |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. | Changes in serum levels of a panel of 41 cytokines will be compared to baseline levels using Luminex methods (HCYTOMAG-60K-PX41 kit from EMD Millipore). No pre-specified threshold was set for biological significance, and the number of cytokines showing a statistically significant (p=<0.05) change from time 0 for each group will be reported. The number of cytokines with significant changes is taken from a comparison of the mean levels in each of the groups, not at the level of individual participants. | Pre-treatment, 4 hours and 24 hours post-treatment |
| Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. | Changes in expression levels of approximately 770 genes involved in innate immunity will be measured in peripheral blood mononuclear cells (PBMC) before and after treatment. The number of transcripts with significant changes is taken from a comparison of the mean levels in each of the groups, not at the individual participant level. No pre-determined threshold was set for the biological significance of these changes. | Pre-treatment, 4 hours and 24 hours post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Blood Counts (CBC) | CBCs will be performed before treatment and 24 hrs later | Pre-treatment (0hrs), 24 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Adrian J Wolstenholme, PhD | University of Georgia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Georgia | Athens | Georgia | 30602 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34090504 | Derived | Wilson NE, Reaves BJ, Wolstenholme AJ. Lack of detectable short-term effects of a single dose of ivermectin on the human immune system. Parasit Vectors. 2021 Jun 5;14(1):304. doi: 10.1186/s13071-021-04810-6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ivermectin | Ivermectin will be administered once at 150mcg/kg, orally. Ivermectin: 150 mcg/kg ivermectin, by mouth. |
| FG001 | Control | An oral placebo will be administered once Placebo: An oral placebo will be administered, once |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ivermectin | Ivermectin will be administered once at 150mcg/kg, orally. Ivermectin: 150 mcg/kg ivermectin, by mouth. |
| BG001 | Control | An oral placebo will be administered once Placebo: An oral placebo will be administered, once |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. | Changes in serum levels of a panel of 41 cytokines will be compared to baseline levels using Luminex methods (HCYTOMAG-60K-PX41 kit from EMD Millipore). No pre-specified threshold was set for biological significance, and the number of cytokines showing a statistically significant (p=<0.05) change from time 0 for each group will be reported. The number of cytokines with significant changes is taken from a comparison of the mean levels in each of the groups, not at the level of individual participants. | Cytokines were measured in sera using the HCYTOMAG-60K-PX41 kit from EMD Millipore. The numbers reported are the number of cytokines with statistically significant changes ( p = <0.05) from pre-treatment levels. | Posted | Number | Cytokines changed from t=0 | Pre-treatment, 4 hours and 24 hours post-treatment | Cytokines | Cytokines |
|
1 day following administration of the drug/placebo
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ivermectin | Ivermectin will be administered once at 150mcg/kg, orally. Ivermectin: 150 mcg/kg ivermectin, by mouth. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Minor gastrointestinal upset | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Adrian Wolstenholme | University of Georgia | 706 542 2404 | adrianw@uga.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Sep 27, 2017 | Nov 28, 2018 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D007559 | Ivermectin |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Other |
An oral placebo will be administered, once |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Ivermectin will be administered once at 150mcg/kg, orally. Ivermectin: 150 mcg/kg ivermectin, by mouth. 4 hrs post-treatment |
| OG001 | Ivermectin 24 Hrs | Ivermectin will be administered once at 150mcg/kg, orally. Ivermectin: 150 mcg/kg ivermectin, by mouth.24 hrs post-treatment |
| OG002 | Control 4 Hrs | An oral placebo will be administered once Placebo: An oral placebo will be administered, once. Sera collected 4hrs post-treatment |
| OG003 | Control 24 Hrs | An oral placebo will be administered once Placebo: An oral placebo will be administered, once. Sera collected 24hrs post-treatment |
|
|
|
| Primary | Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. | Changes in expression levels of approximately 770 genes involved in innate immunity will be measured in peripheral blood mononuclear cells (PBMC) before and after treatment. The number of transcripts with significant changes is taken from a comparison of the mean levels in each of the groups, not at the individual participant level. No pre-determined threshold was set for the biological significance of these changes. | Levels of 770 messenger RNAs (mRNAs) were assayed in PBMC isolated from study participants using the Human Nanostring Myeloid cell panel. | Posted | Number | Transcripts signicantly changed from t=0 | Pre-treatment, 4 hours and 24 hours post-treatment |
|
|
|
|
| Secondary | Complete Blood Counts (CBC) | CBCs will be performed before treatment and 24 hrs later | Posted | Mean | Standard Error | Million cells/mL | Pre-treatment (0hrs), 24 hours |
|
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 1 |
| 8 |
| EG001 | Control | An oral placebo will be administered once Placebo: An oral placebo will be administered, once | 0 | 4 | 0 | 4 | 1 | 4 |
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| Lymphocytes |
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| Monocytes |
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| Eosinophils |
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| Basophils |
|