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CompletedNCT03459794Updated Jul 12, 2019Results posted

Ivermectin and Human Immunity

An Early Phase 1 interventional study of Ivermectin and Placebo in Ivermectin, sponsored by University of Georgia. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-07-12.

Sponsored by University of Georgia · Early Phase 1, Interventional, and Basic science

Phase
Early Phase 1
Study type
Interventional
Enrollment
12
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Ivermectin
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Weight over 110 pounds and under 185 pounds

Exclusion criteria

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
04

Study design

Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
12 participants (actual)

Study arms

  • Active comparator
    Ivermectin

    Ivermectin will be administered once at 150mcg/kg, orally.

    Drug: Ivermectin

  • Placebo comparator
    Control

    An oral placebo will be administered once

    Other: Placebo

Interventions

  • DrugIvermectin

    150 mcg/kg ivermectin, by mouth.

  • OtherPlacebo

    An oral placebo will be administered, once

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. Complete Blood Counts (CBC)

    CBCs will be performed before treatment and 24 hrs later

    Time frame: Pre-treatment (0hrs), 24 hours

06

Results

Posted Jul 12, 2019

Participant flow

Participant flow — Overall Study
MilestoneIvermectinControl
Started84
Completed84
Not completed00

Outcome measures

PrimaryThe 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
Reported as:
Number · Cytokines changed from t=0
The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded.
Cytokines changed from t=0Ivermectin 4hrsIvermectin 24 HrsControl 4 HrsControl 24 Hrs
The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded.0000
Statistical analysis
  • Ivermectin 4hrs vs Ivermectin 24 Hrs vs Control 4 Hrs vs Control 24 Hrs ·
PrimaryNumber 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
Reported as:
Number · Transcripts signicantly changed from t=0
Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels.
Transcripts signicantly changed from t=0Ivermectin 4hrsIvermectin 24 HrsControl 4 HrsControl 24 Hrs
Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels.00100
Statistical analysis
  • Ivermectin 4hrs vs Ivermectin 24 Hrs vs Control 4 Hrs vs Control 24 Hrs ·
SecondaryComplete Blood Counts (CBC)

CBCs will be performed before treatment and 24 hrs later

Time frame:
Pre-treatment (0hrs), 24 hours
Reported as:
Mean · Million cells/mL
Complete Blood Counts (CBC)
Million cells/mLIvermectin 0 HrsIvermectin 24 HrsControl 0 HrsControl 24 Hrs
Neutrophils3.069 ± 0.3533.341 ± 0.4262.940 ± 0.183.358 ± 0.47
Lymphocytes1.753 ± 0.221.864 ± 0.1511.833 ± 0.1612.075 ± 0.175
Monocytes0.483 ± 0.0450.403 ± 0.0570.373 ± 0.040.375 ± 0.034
Eosinophils0.208 ± 0.0550.205 ± 0.0470.158 ± 0.0150.170 ± 0.018
Basophils0.04 ± 0.0080.046 ± 0.0060.048 ± 0.0080.048 ± 0.0005
Statistical analysis
  • Ivermectin 0 Hrs vs Ivermectin 24 Hrs vs Control 0 Hrs vs Control 24 Hrs · t-test, 1 sided · p = <0.05

Adverse events

Collected over 1 day following administration of the drug/placebo. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ivermectin0/8 (0%)0/8 (0%)1/8 (12.5%)
Control0/4 (0%)0/4 (0%)1/4 (25%)
Most frequent other events
Most frequent other events
EventIvermectinControl
Minor gastrointestinal upsetGastrointestinal disorders1/81/4

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)IvermectinControlTotal
<=18 years000
Between 18 and 65 years8412
>=65 years000
Sex: Female, Male
Sex: Female, Male(Participants)IvermectinControlTotal
Female549
Male303
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)IvermectinControlTotal
Hispanic or Latino112
Not Hispanic or Latino639
Unknown or Not Reported101
Race (NIH/OMB)
Race (NIH/OMB)(Participants)IvermectinControlTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White7411
More than one race000
Unknown or Not Reported101
Region of Enrollment
Region of Enrollment(participants)IvermectinControlTotal
United States8412
07

Study locations

1 site
  • University of Georgia
    Athens, Georgia 30602, United States
08

References and documents

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. PubMed 34090504 ↗

Study documents

  • Protocol, analysis plan and consent form · Sep 27, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03459794
Lead sponsor
University of Georgia
Responsible party
Adrian Wolstenholme (Professor, University of Georgia) — Principal investigator
First posted
Mar 9, 2018
Start date
Feb 12, 2018
Primary completion
Apr 9, 2018
Completion
Nov 30, 2018
Results posted
Jul 12, 2019
Last update
Jul 12, 2019

Study contacts

Adrian J Wolstenholme, PhD
principal investigator · University of Georgia

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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