Ivermectin
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGIvermectin
150 mcg/kg ivermectin, by mouth.
OTHERPlacebo
An oral placebo will be administered, once
Sponsors
University of Georgia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Weight over 110 pounds and under 185 pounds
Exclusion criteria
* Pregnancy or nursing mothers. * Immunosuppressed individuals. * Hypersensitivity to ivermectin, cellulose, starch, magnesium stearate, butylated hydroxyanisole, or citric acid powder (inert ingredients of Stromectol). * Recent (last 3 years) travel to West or Central Africa, or any other country where onchocerciasis is present * Hepatitis/HIV * Currently taking warfarin * Lactose intolerance (Lactose present in placebo) * Currently taking Steroid medications (inhaled, oral or injection) * Currently taking Barbiturates, Benzodiazepines such as Xanax or Klonopin, Valproic acid (Lithium), Calcium channel blockers, Statins (cholesterol medication) * Liver or renal dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. | Pre-treatment, 4 hours and 24 hours post-treatment | 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. |
| Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. | Pre-treatment, 4 hours and 24 hours post-treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Blood Counts (CBC) | Pre-treatment (0hrs), 24 hours | CBCs will be performed before treatment and 24 hrs later |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ivermectin Ivermectin will be administered once at 150mcg/kg, orally.
Ivermectin: 150 mcg/kg ivermectin, by mouth. | 8 |
| Control An oral placebo will be administered once
Placebo: An oral placebo will be administered, once | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Ivermectin | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 8 participants | 4 participants | 12 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 1 / 8 | 1 / 4 |
| serious Total, serious adverse events | 0 / 8 | 0 / 4 |
Outcome results
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.
Time frame: Pre-treatment, 4 hours and 24 hours post-treatment
Population: Levels of 770 messenger RNAs (mRNAs) were assayed in PBMC isolated from study participants using the Human Nanostring Myeloid cell panel.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ivermectin 4hrs | Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. | 0 Transcripts signicantly changed from t=0 |
| Ivermectin 24 Hrs | Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. | 0 Transcripts signicantly changed from t=0 |
| Control 4 Hrs | Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. | 10 Transcripts signicantly changed from t=0 |
| Control 24 Hrs | Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. | 0 Transcripts signicantly changed from t=0 |
Comparison: All measurements were compared to the same treated/control group at t=0, before the drug or placebo was administered. We compared the expression levels for each transcript, using the mean levels in each group, not at the individual participant level.
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.
Time frame: Pre-treatment, 4 hours and 24 hours post-treatment
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ivermectin 4hrs | The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. | 0 Cytokines changed from t=0 |
| Ivermectin 24 Hrs | The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. | 0 Cytokines changed from t=0 |
| Control 4 Hrs | The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. | 0 Cytokines changed from t=0 |
| Control 24 Hrs | The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. | 0 Cytokines changed from t=0 |
Comparison: All measurements were compared to the same group at t=0, that is before the drug or placebo was administered. We compared the expression levels for each transcript, using the mean levels in each group, not at the individual participant level.
Secondary
Complete Blood Counts (CBC)
CBCs will be performed before treatment and 24 hrs later
Time frame: Pre-treatment (0hrs), 24 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivermectin 4hrs | Complete Blood Counts (CBC) | Eosinophils | 0.208 Million cells/mL | Standard Error 0.055 |
| Ivermectin 4hrs | Complete Blood Counts (CBC) | Lymphocytes | 1.753 Million cells/mL | Standard Error 0.22 |
| Ivermectin 4hrs | Complete Blood Counts (CBC) | Basophils | 0.04 Million cells/mL | Standard Error 0.008 |
| Ivermectin 4hrs | Complete Blood Counts (CBC) | Monocytes | 0.483 Million cells/mL | Standard Error 0.045 |
| Ivermectin 4hrs | Complete Blood Counts (CBC) | Neutrophils | 3.069 Million cells/mL | Standard Error 0.353 |
| Ivermectin 24 Hrs | Complete Blood Counts (CBC) | Monocytes | 0.403 Million cells/mL | Standard Error 0.057 |
| Ivermectin 24 Hrs | Complete Blood Counts (CBC) | Eosinophils | 0.205 Million cells/mL | Standard Error 0.047 |
| Ivermectin 24 Hrs | Complete Blood Counts (CBC) | Basophils | 0.046 Million cells/mL | Standard Error 0.006 |
| Ivermectin 24 Hrs | Complete Blood Counts (CBC) | Lymphocytes | 1.864 Million cells/mL | Standard Error 0.151 |
| Ivermectin 24 Hrs | Complete Blood Counts (CBC) | Neutrophils | 3.341 Million cells/mL | Standard Error 0.426 |
| Control 4 Hrs | Complete Blood Counts (CBC) | Monocytes | 0.373 Million cells/mL | Standard Error 0.04 |
| Control 4 Hrs | Complete Blood Counts (CBC) | Neutrophils | 2.940 Million cells/mL | Standard Error 0.18 |
| Control 4 Hrs | Complete Blood Counts (CBC) | Lymphocytes | 1.833 Million cells/mL | Standard Error 0.161 |
| Control 4 Hrs | Complete Blood Counts (CBC) | Eosinophils | 0.158 Million cells/mL | Standard Error 0.015 |
| Control 4 Hrs | Complete Blood Counts (CBC) | Basophils | 0.048 Million cells/mL | Standard Error 0.008 |
| Control 24 Hrs | Complete Blood Counts (CBC) | Eosinophils | 0.170 Million cells/mL | Standard Error 0.018 |
| Control 24 Hrs | Complete Blood Counts (CBC) | Lymphocytes | 2.075 Million cells/mL | Standard Error 0.175 |
| Control 24 Hrs | Complete Blood Counts (CBC) | Neutrophils | 3.358 Million cells/mL | Standard Error 0.47 |
| Control 24 Hrs | Complete Blood Counts (CBC) | Monocytes | 0.375 Million cells/mL | Standard Error 0.034 |
| Control 24 Hrs | Complete Blood Counts (CBC) | Basophils | 0.048 Million cells/mL | Standard Error 0.0005 |
p-value: <0.05t-test, 1 sided