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Eosinophils in Insulin Sensitivity in Humans

Overview

About this study

 

The goal of this proposal is to highlight a potentially pivotal role of EOS in human metabolism. This pilot project will initiate future investigations demonstrating AT-EOS involvement in insulin sensitivity (IS). These data will be innovative, and of great clinical importance in the era of FDA-approved biologic drugs treating many eosinophilic-driven diseases. These drugs lack comprehensive assessment of their impact on metabolic health. Our central hypothesis is that elimination of circulating EOS will negatively affect systemic inflammation and plasma adipokines levels (low adiponectin, high leptin) resulting in impaired glucose metabolism, all central features of IR. Our team is well suited to perform these studies based on our experience in measuring in vivo IS in humans. We propose the following specific aim:

Aim 1: To determine the metabolic effects of decreasing circulating EOS in healthy subjects. Mepolizumab is an FDA-approved drug that selectively reduces circulating EOS12. We have an IND exemption approved by the FDA to use mepolizumab in healthy subjects to test our central hypothesis. This pilot study will lay the foundation to further investigate the impact of Mepolizumab on AT-EOS content and tissue homeostasis (NIH R01 proposal). Elucidating a role for EOS in metabolic homeostasis will advance the role of future immunotherapeutic agents in the treatment of IR and prevent development of obesity-related complications.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age, 18-60 years old.
  • Ability to sign informed consent form.
  • Body mass index (BMI), 22-29 kg/m^2.
  • Matsuda insulin sensitivity index (ISI), lean > 7.
  • Fasting glucose < 100 mg/dL.
  • HgbA1c < 5.7%.
  • Highly sensitive C-reactive protein < 2 mg/dL.

Exclusion Criteria:

  • Any prescription for oral or inhaled glucocorticoid, antidiabetic medications, montelukast.
  • St. John’s wort supplement.
  • Evidence of pre-diabetes (fasting glucose > 100 mg/dL or HgbA1c ≥ 5.7%).
  • Evidence of diabetes mellitus.
  • Diagnosis of asthma, eosinophilic disease, or atopic syndrome.
  • Presence of acute illness.
  • History of liver disease (alanine aminotransferase level > 1.5 × upper limit of normal, bilirubin level > 1.5 × upper limit of normal).
  • History of regular alcohol consumption within 6 months of the study defined as an average of weekly intake of > 14 units for females, and > 21 units for males.
  • History of biliary abnormalities (except for Gilbert’s syndrome or asymptomatic gallstones).
  • uncontrolled metabolic disease, including renal disease.
  • Heart disease: ECG-documented abnormalities such as QT interval corrected using Fridericia’s formula > 450 milliseconds).
  • Low hemoglobin or hematocrit.
  • Current participation in a weight-loss regimen, with a weight loss >10% total body weight in the last 6 months).
  • Known pre-existing helminth infestation..
  • Smoking history in the last 6 months (tobacco, nicotine-containing products including e-cigarettes)
  • Pregnant or lactating.
  • Personal history of gastric bypass surgery.
  • History of sensitivity to study medication or its components.
  • Previous participation in a clinical trial with an investigational product in the past 30 days, or 5 half-lives, or twice the duration of the biological effect of the investigational drug (whichever is longest).
  • Exposed to more than 4 new chemical entities within 12 months before study enrollment.
  • Any other condition or event considered exclusionary by the PI and the study physician.

Eligibility last updated 2/17/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Elena Anna De Filippis, M.D., Ph.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Keegan Stewart M.S.

(480) 301-4164

Stewart.Keegan@mayo.edu

More information

Publications

Publications are currently not available

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CLS-20559474

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