Detection of miRNAs in HPA Axis Function in Healthy Subjects

The proposed study will test dexamethasone effect on miRNA profile in healthy humans. As our data indicate that miRNA levels change over time, the investigators will study the time course of miRNA response to 1 mg IV dexamethasone within 60 minutes after injection. Dexamethasone is used routinely in human subjects for the treatment of inflammatory conditions and as a diagnostic tool in the evaluation of excess cortisol secretion (Cushing's syndrome). For the latter, 1 mg dexamethasone is given orally at midnight. Oral formula absorption in the gut can range from 20 to 60 minutes due to the presence of food and other factors. IV administration will bypass this variability and ensure an accurate and reproducible time-course study. The investigators will compare miRNA expression before and after dexamethasone treatment. The investigators will follow miRNA expression dynamics over a 1-hour time course to identify peak expression levels and to correlate miRNA expression with circulating dexamethasone levels. Dexamethasone and miRNA levels will be checked at baseline just before injection and then at 15, 30, 45, and 60 minutes after injection. Dexamethasone level is taken to verify treatment and to correlate it with miRNA expression.

Study Overview

• Status: Terminated
• Conditions: Dexamethasone Effect on miRNA Profile in Healthy Humans
• Intervention / Treatment: Drug: Dexamethasone 4mg

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults age ≥ 18

Exclusion Criteria:

• Pregnancy
• Presence of a disease that affects HPA axis function
• Current use of medications that affect cortisol secretion, such as opioid pain medication, anti-fungal agents, anti-epileptic agents, and glucocorticoids, including hydrocortisone, prednisone, dexamethasone, steroid-containing inhalers, and steroid injected into the joints
• History of adverse event related to use of glucocorticoids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexamthesone; Single arm study in which all healthy controls will receive 1 mg of dexamethasone intravenous (IV) injection.	Drug: Dexamethasone 4mg; 1 mg IV dexamethasone will be pushed and miRNA levels will be checked at baseline just before injection and then at 15, 30, 45, and 60 minutes after injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (Time of Injection) miRNA Levels and 60 Minutes After Injection	The change of miRNA levels in blood between time of injection (baseline) and 60 minutes after injection. Expressed as miRx ratio: miR expression level normalized to miR7-2-1 expression level and divided by miRx expression at baseline (T0).	Baseline and 60 minutes

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Anat Benshlomo, MD, Cedars-Sinai Medical Center

Publications and helpful links

General Publications

• Yamamoto M, Ben-Shlomo A, Kameda H, Fukuoka H, Deng N, Ding Y, Melmed S. Somatostatin receptor subtype 5 modifies hypothalamic-pituitary-adrenal axis stress function. JCI Insight. 2018 Oct 4;3(19):e122932. doi: 10.1172/jci.insight.122932.
• Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A, Brownstein MJ, Tuschl T, Margalit H. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res. 2005 May 12;33(8):2697-706. doi: 10.1093/nar/gki567. Print 2005.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2019
• Primary Completion (Actual): July 24, 2019
• Study Completion (Actual): July 24, 2019

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: Pro57715

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