Ivermectin and Human Immunity

The Effects of Ivermectin on Human Innate Immunity Against Filarial Parasites

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.

Study Overview

• Status: Completed
• Conditions: Ivermectin
• Intervention / Treatment: Drug: Ivermectin; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Athens, Georgia, United States, 30602
      • University of Georgia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ivermectin; Ivermectin will be administered once at 150mcg/kg, orally.	Drug: Ivermectin; 150 mcg/kg ivermectin, by mouth.
Placebo Comparator: Control; An oral placebo will be administered once	Other: Placebo; An oral placebo will be administered, once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Blood Counts (CBC)	CBCs will be performed before treatment and 24 hrs later	Pre-treatment (0hrs), 24 hours

Collaborators and Investigators

• Sponsor: University of Georgia
• Investigators: Principal Investigator: Adrian J Wolstenholme, PhD, University of Georgia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): April 9, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: March 2, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiparasitic Agents; Ivermectin
• Other Study ID Numbers: STUDY00005069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No