Glucocorticoid Inflammation Paradox in Human Skeletal Muscle
| Status: | Recruiting |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 60 - 80 |
| Updated: | 5/20/2018 |
| Start Date: | June 1, 2018 |
| End Date: | December 1, 2019 |
| Contact: | Kate M Randolph, BS |
| Email: | krandolph@tamu.edu |
| Phone: | 409-223-7891 |
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.
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.
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.
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.
Inclusion Criteria:
1. Ages: 60 - 80 years.
2. For men only: Eugonadal men, with a basal serum testosterone level for men within the
normal range for the assay.
3. For women only: women must be post-menopausal.
4. Availability of transportation (i.e., subjects must be able to provide their own
transportation to TAMU HCRF).
5. Ability to fast for 12 hours before each of the study visits
Exclusion Criteria:
1. Use of anticoagulant due to the risk of bleeding during the muscle biopsy procedure.
2. Current use or history of recent use of anabolic steroids or glucocorticoids (within 3
months).
3. Use of anti-bone-resorptive agents such as bisphosphonates, parathyroid hormone, or
calcitonin.
4. Use of live virus vaccines in the past 30 days.
5. History of stroke.
6. History of angina that occurs with exertion or at rest or a myocardial infarction
within the last 12 months.
7. Diagnosed systemic viral, bacterial, or fungal infections.
8. Any established major medical illness such as chronic obstructive pulmonary disease,
or untreated sleep apnea.
9. Subjects with minor, acute inflammatory illnesses such as colds will be excluded until
the acute illness has resolved.
10. Uncontrolled endocrine or metabolic disease (e.g. liver disease, renal disease,
diabetes).
11. History or current diagnosis of type 1 or type 2 diabetes. High doses of
glucocorticoids can increase insulin resistance and exacerbate diabetes.
12. 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.
13. 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.
14. History of seizure disorder.
15. History of tuberculosis.
16. Current diagnosis of peptic ulcer disease, gastritis, or non-ulcer dyspepsia.
17. Current diagnosis of mental illness.
18. Current diagnosis of cognitive impairment.
19. Subjects with sleep disturbances.
20. Current self-reported immunosuppressive disorder.
21. Any other condition or event considered exclusionary by the PI and covering physician.
We found this trial at
1
site
College Station, Texas 77843
Principal Investigator: Melinda Sheffield-Moore, PhD
Phone: 409-223-7891
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