Clinical trial NCT03459794: Ivermectin and Human Immunity
Official title: The Effects of Ivermectin on Human Innate Immunity Against Filarial Parasites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Ivermectin
Lead sponsor: University of Georgia
Sponsor class: OTHER
First posted: 2018-03-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded.
timeFrame: Pre-treatment, 4 hours and 24 hours post-treatment
measure: Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels.
timeFrame: Pre-treatment, 4 hours and 24 hours post-treatment
Secondary outcomes:
measure: Complete Blood Counts (CBC)
timeFrame: Pre-treatment (0hrs), 24 hours
Other outcomes:
Locations:
city: Athens
country: United States
facility: University of Georgia
state: Georgia
Study officials:
affiliation: University of Georgia
name: Adrian J Wolstenholme, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.