Ivermectin and Human Immunity

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.

• Ivermectin (Drug): 150 mcg/kg ivermectin, by mouth.
• Placebo (Other): An oral placebo will be administered, once

Primary outcomes

• 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 outcomes

• Complete Blood Counts (CBC) [Pre-treatment (0hrs), 24 hours]: CBCs will be performed before treatment and 24 hrs later

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

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

Participant flow

Outcome results

• The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded. (Primary), Number, Cytokines changed from t=0: Ivermectin 4hrs 0; Ivermectin 24 Hrs 0; Control 4 Hrs 0; Control 24 Hrs 0
• Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels. (Primary), Number, Transcripts signicantly changed from t=0: Ivermectin 4hrs 0; Ivermectin 24 Hrs 0; Control 4 Hrs 10; Control 24 Hrs 0
• Complete Blood Counts (CBC) (Secondary), Mean, Million cells/mL: Ivermectin 0 Hrs 3.069 +/- 0.353; Ivermectin 24 Hrs 3.341 +/- 0.426; Control 0 Hrs 2.940 +/- 0.18; Control 24 Hrs 3.358 +/- 0.47 (p <0.05)

Adverse events

Time frame: 1 day following administration of the drug/placebo

Other adverse events by term

• Results publication: 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. PMID 34090504

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form (PDF, 2017-09-27)

• Adrian J Wolstenholme, PhD, Principal investigator, University of Georgia