Detection of miRNAs in HPA Axis Function in Healthy Subjects

• Sponsor: Cedars-Sinai Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04066647
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 2.5
• Patients Per Site Per Month: 2.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dexamethasone Effect on miRNA Profile in Healthy Humans	Drug: Dexamethasone 4mg	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Detection of miRNAs in HPA Axis Function in Healthy Subjects
• Actual Study Start Date: May 9, 2019
• Actual Primary Completion Date: Jul 24, 2019
• Actual Study Completion Date: Jul 24, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline (Time of Injection) miRNA Levels and 60 Minutes After Injection [Baseline and 60 minutes]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048

Sponsors and Collaborators

• Cedars-Sinai Medical Center

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jun 6, 2019
• Informed Consent Form - Jun 25, 2019

More Information

Publications

• 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. Print 2005.
• 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). pii: 122932. doi: 10.1172/jci.insight.122932.

• Responsible Party: Anat Ben-Shlomo, MD, Staff Physician, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT04066647
• Other Study ID Numbers: Pro57715
• First Posted: Aug 26, 2019
• Last Update Posted: Jul 17, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Dexamethasone

Study Results

Participant Flow

Arm/Group Title	Dexamthesone
Arm/Group Description	Single arm study in which all healthy controls will receive 1 mg of dexamethasone intravenous (IV) injection. 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.
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Dexamethesone
Arm/Group Description	Single arm study in which all healthy controls will receive 1 mg of dexamethasone intravenous (IV) injection. Dexamethasone 4mg: 1 mg IV dexamethasone will be pushed and miRNA levels will be checked at baseline just before injection and then at 60 minutes after injection.
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	31
Sex: Female, Male (Count of Participants)
Female	5 71.4%
Male	2 28.6%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (Time of Injection) miRNA Levels and 60 Minutes After Injection
Description	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).
Time Frame	Baseline and 60 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethesone
Arm/Group Description	Single arm study in which all healthy controls will receive 1 mg of dexamethasone intravenous (IV) injection. 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.
Measure Participants	7
Mean (Standard Deviation) [percentage of change]	0.939288216 (0.762951729)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexamethesone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	t-test, 2 sided
	Comments	2 tailed, unpaired t test with Bonferroni correction
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.93928821
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	2.5 months
Arm/Group Title	Dexamethesone
Arm/Group Description	Single arm study in which all healthy controls will receive 1 mg of dexamethasone intravenous (IV) injection. Dexamethasone 4mg: 1 mg IV dexamethasone will be pushed and miRNA levels will be checked at baseline just before injection and then at 60 minutes after injection.
All Cause Mortality
	Dexamethesone
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Dexamethesone
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Dexamethesone
	Affected / at Risk (%)	# Events
Total	0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.