Detection of miRNAs in HPA Axis Function in Healthy Subjects

NCT04066647 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: Pro57715
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dexamethasone Effect on miRNA Profile in Healthy Humans

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Dexamthesone

EXPERIMENTAL

Single arm study in which all healthy controls will receive 1 mg of dexamethasone intravenous (IV) injection.

Drug: Dexamethasone 4mg

Interventions

Dexamethasone 4mg DRUG

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.

Dexamthesone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults age ≥ 18

You may not qualify if:

• 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (2)

• 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.

  PMID: 30282821 BACKGROUND

• 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.

  PMID: 15891114 BACKGROUND

MeSH Terms

Interventions

Dexamethasone

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Kacey Haptonstall
• Organization: Cedars Sinai Medical Center

kacey.haptonstall@cshs.org

424-315-4489

Study Officials

• Anat Benshlomo, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: August 26, 2019
• Study Start: May 9, 2019
• Primary Completion: July 24, 2019
• Study Completion: July 24, 2019
• Last Updated: July 17, 2020
• Results First Posted: July 17, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)