Back to resultsGlucocorticoid Inflammation Paradox in Human Skeletal Muscle
Primary Purpose
Aging
Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Methylprednisolone
Sponsored by
About this trial
This is an interventional treatment trial for Aging focused on measuring glucocorticoids, aging, NFKB, Medrol, methylprednisolone
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- Current diagnosis of peptic ulcer disease, gastritis, or non-ulcer dyspepsia.
- Current diagnosis of mental illness.
- Current diagnosis of cognitive impairment.
- Subjects with sleep disturbances.
- Current self-reported immunosuppressive disorder.
- Any other condition or event considered exclusionary by the PI and covering physician.
Sites / Locations
- Texas A&M University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Methylprednisolone
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
Lean Body Mass as measured by Dual Energy X-Ray Absorptiometry on day 0
Lean body mass will be measured using a Hologic DEXA on day 0.
Lean Body Mass as measured by Dual Energy X-Ray Absorptiometry on day 6
Lean body mass will be measured using a Hologic DEXA on day 6, after the 6 day methylprednisolone treatment.
Fat Mass as measured by Dual Energy X-Ray Absorptiometry on day 0
Fat mass will be measured using a Hologic DEXA on day 0.
Fat Mass as measured by Dual Energy X-Ray Absorptiometry on day 6
Fat mass will be measured using a Hologic DEXA on day 6, after the 6 day methylprednisolone treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03529929
Brief Title
Glucocorticoid Inflammation Paradox in Human Skeletal Muscle
Official Title
Glucocorticoid Inflammation Paradox in Human Skeletal Muscle
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Withdrawn
Why Stopped
withdrawn
Study Start Date
June 1, 2019 (Anticipated)
Primary Completion Date
May 1, 2020 (Anticipated)
Study Completion Date
December 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Texas A&M University
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
Healthy male and female individuals ages 60 - 80 (n=10) will be studied before and after 6 days of treatment with self-administered daily oral methylprednisolone.
Subjects will report to the Texas A&M Human Clinical Research Facility (HCRF) for testing before (day 0) and after (day 6) methylprednisolone intervention. Each visit will consist of determination of lean and fat mass using DEXA and a single muscle biopsy. Blood will be collected (up to 15ml) at screening, baseline and the conclusion of the study to measure metabolites and hormones. Phone calls will be made to subjects mid-week (day 3) during the study period to ensure compliance and continued consent.
This will be an unblinded study. All participants will receive methylprednisolone treatment.
Therapeutic Interventions. Methylprednisolone (Medrol®) dose pack. Methylprednisolone is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Therapeutic methylprednisolone is approved for clinical use for a variety of disorders. Medrol®, the agent to be used in this study, is manufactured by Pfizer.
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, Table 1 above). This methylprednisolone dosing regimen is commonly prescribed for the treatment of inflammation associated with a number of pathologies, including arthritic, respiratory, and neoplastic diseases. The Medrol® pack has clear instructions on how to administer the tablets and participants will be given additional instruction to ensure understanding for proper self-administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aging
Keywords
glucocorticoids, aging, NFKB, Medrol, methylprednisolone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Methylprednisolone
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
Medrol Dose Pack, Medrol
Intervention Description
6 day dosing as dictated by Medrol 6 Day Dose Pack
Primary Outcome Measure Information:
Title
Oxidative Phosphorylation Capacity measured by high resolution tissue respirometry on day 0
Description
Oxidative Phosphorylation will be measured in muscle tissue using high resolution respirometry (Oroboros O2K) on day 0.
Time Frame
day 0
Title
Oxidative Phosphorylation Capacity measured by high resolution tissue respirometry on day 6
Description
Oxidative Phosphorylation will be measured in muscle tissue using high resolution respirometry (Oroboros O2K) on day 6, after the 6 day methylpredinsolone treatment.
Time Frame
day 6
Title
Expression level of NFKB Inducing Kinase (NIK) in tissue measured by real time PCR on day 0
Description
NIK expression will be measured in muscle tissue using real time PCR on day 0.
Time Frame
day 0
Title
Expression level of NFKB Inducing Kinase (NIK) in tissue measured by real time PCR on day 6
Description
NIK expression will be measured in muscle tissue using real time PCR on day 6, after the 6 day methylprednisolone treatment.
Time Frame
day 6
Secondary Outcome Measure Information:
Title
Lean Body Mass as measured by Dual Energy X-Ray Absorptiometry on day 0
Description
Lean body mass will be measured using a Hologic DEXA on day 0.
Time Frame
day 0
Title
Lean Body Mass as measured by Dual Energy X-Ray Absorptiometry on day 6
Description
Lean body mass will be measured using a Hologic DEXA on day 6, after the 6 day methylprednisolone treatment.
Time Frame
day 6
Title
Fat Mass as measured by Dual Energy X-Ray Absorptiometry on day 0
Description
Fat mass will be measured using a Hologic DEXA on day 0.
Time Frame
day 0
Title
Fat Mass as measured by Dual Energy X-Ray Absorptiometry on day 6
Description
Fat mass will be measured using a Hologic DEXA on day 6, after the 6 day methylprednisolone treatment.
Time Frame
day 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Current diagnosis of peptic ulcer disease, gastritis, or non-ulcer dyspepsia.
Current diagnosis of mental illness.
Current diagnosis of cognitive impairment.
Subjects with sleep disturbances.
Current self-reported immunosuppressive disorder.
Any other condition or event considered exclusionary by the PI and covering physician.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melinda Sheffield-Moore, PhD
Organizational Affiliation
Texas A&M University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas A&M University
City
College Station
State/Province
Texas
ZIP/Postal Code
77843
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Glucocorticoid Inflammation Paradox in Human Skeletal Muscle
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