Glucocorticoid Inflammation Paradox in Human Skeletal Muscle

NCT03529929 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: IRB2017-0883
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In this project, we propose to investigate the metabolic consequences of glucocorticoid therapy, given orally as a 6 day Medrol Dose pack, on human skeletal muscle as measured by western blotting and PCR and skeletal muscle mitochondrial capacity as measured by High-Resolution Respirometry in healthy individuals. Medrol is an FDA approved drug with many clinical indications.

Conditions

Aging

Keywords

glucocorticoids; aging; NFKB; Medrol; methylprednisolone

Outcome Measures

Primary Outcomes (4)

• Oxidative Phosphorylation Capacity measured by high resolution tissue respirometry on day 0

  Oxidative Phosphorylation will be measured in muscle tissue using high resolution respirometry (Oroboros O2K) on day 0.

  day 0

• Oxidative Phosphorylation Capacity measured by high resolution tissue respirometry on day 6

  Oxidative Phosphorylation will be measured in muscle tissue using high resolution respirometry (Oroboros O2K) on day 6, after the 6 day methylpredinsolone treatment.

  day 6

• Expression level of NFKB Inducing Kinase (NIK) in tissue measured by real time PCR on day 0

  NIK expression will be measured in muscle tissue using real time PCR on day 0.

  day 0

• Expression level of NFKB Inducing Kinase (NIK) in tissue measured by real time PCR on day 6

  NIK expression will be measured in muscle tissue using real time PCR on day 6, after the 6 day methylprednisolone treatment.

  day 6

Secondary Outcomes (4)

• Lean Body Mass as measured by Dual Energy X-Ray Absorptiometry on day 0

  day 0

• Lean Body Mass as measured by Dual Energy X-Ray Absorptiometry on day 6

  day 6

• Fat Mass as measured by Dual Energy X-Ray Absorptiometry on day 0

  day 0

• Fat Mass as measured by Dual Energy X-Ray Absorptiometry on day 6

  day 6

Study Arms (1)

Methylprednisolone

EXPERIMENTAL

Methylprednisolone glucocorticoid Medrol Dose Pack Medrol is supplied as white tablets, of 4mg each. The tablets come in a commercially produced blister pack with instructions for each day of the 6 day dosing on the packaging. Subjects will receive a standard 6-day, graded dosing regimen of methylprednisolone (24mg, 20mg, 16mg, 12mg, 8mg, and 4 mg on days 1 through 6 respectively).

Drug: Methylprednisolone

Interventions

Methylprednisolone DRUG

6 day dosing as dictated by Medrol 6 Day Dose Pack

Also known as: Medrol Dose Pack, Medrol

Methylprednisolone

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages: 60 - 80 years.
• For men only: Eugonadal men, with a basal serum testosterone level for men within the normal range for the assay.
• For women only: women must be post-menopausal.
• Availability of transportation (i.e., subjects must be able to provide their own transportation to TAMU HCRF).
• Ability to fast for 12 hours before each of the study visits

You may not qualify if:

• Use of anticoagulant due to the risk of bleeding during the muscle biopsy procedure.
• Current use or history of recent use of anabolic steroids or glucocorticoids (within 3 months).
• Use of anti-bone-resorptive agents such as bisphosphonates, parathyroid hormone, or calcitonin.
• Use of live virus vaccines in the past 30 days.
• History of stroke.
• History of angina that occurs with exertion or at rest or a myocardial infarction within the last 12 months.
• Diagnosed systemic viral, bacterial, or fungal infections.
• Any established major medical illness such as chronic obstructive pulmonary disease, or untreated sleep apnea.
• Subjects with minor, acute inflammatory illnesses such as colds will be excluded until the acute illness has resolved.
• Uncontrolled endocrine or metabolic disease (e.g. liver disease, renal disease, diabetes).
• History or current diagnosis of type 1 or type 2 diabetes. High doses of glucocorticoids can increase insulin resistance and exacerbate diabetes.
• Systolic blood pressure greater than or equal to 160mm Hg or a diastolic blood pressure greater than or equal to 100mm Hg on three consecutive measurements taken at one-week intervals. Glucocorticoids can cause fluid retention that could worsen uncontrolled hypertension. Subjects will be included if they are on two or less blood pressure medications and have a blood pressure below these criteria.
• Subjects who engage in high intensity, elite training on a regular basis will be excluded. Additionally, subjects will be asked to refrain from any exercise during study week.
• History of seizure disorder.
• History of tuberculosis.

Sponsors & Collaborators

• Texas A&M University: lead

Study Sites (1)

Texas A&M University

College Station, Texas, 77843, United States

Location

MeSH Terms

Interventions

Methylprednisolone

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Melinda Sheffield-Moore, PhD

  Texas A&M University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 18, 2018
• Study Start: June 1, 2019
• Primary Completion: May 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 11, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)