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| ID | Type | Description | Link |
|---|---|---|---|
| 3R01AG069858-02W1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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We intend, with this study, to prove that blocking the molecular mechanisms whose blockade prevents VIDD in animals, will indeed prevent the development of VIDD in humans as well. We believe that this evidence will serve as the required basis for proceeding with large, ICU-based clinical trial(s) of a drug to prevent VIDD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tofacitinib | Experimental | Patient will receive two days treatment with tofacitinib prior to the surgery. |
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| Placebo | Placebo Comparator | Patient will receive two days treatment with placebo prior to the surgery. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tofacitinib 10 MG [Xeljanz] | Drug | administered twice daily for two days |
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| Measure | Description | Time Frame |
|---|---|---|
| Prevention of ventilator-induced diaphragm dysfunction by JAK inhibition | Change in the force deficit that develops between the first and second muscle biopsies in the drug-treated vs. placebo groups | 5-6 years |
| Measure | Description | Time Frame |
|---|---|---|
| Increase in muscle strength due to JAK inhibition | Difference in force generated by muscle biopsies taken at time point 1 (pre-mechanical ventilation) from the drug-treated vs placebo groups | 4-5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition. | Compare differences in muscle between the drug-treated and placebo groups in mitochondrial function and oxidative stress (ATP levels, citrate synthase activity, succinate dehydrogenase activity, mitochondrial respiration rate, activity of mitochondial enzymatic compexes). | 4-6 years |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Cheyenne A Clinical Research Coordinator, B.S, M.S | Contact | 3107201689 | csadeghi@stanford.edu |
| Name | Affiliation | Role |
|---|---|---|
| Joseph Shrager, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University Medical Center | Recruiting | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34655959 | Background | Shrager JB, Wang Y, Lee M, Nesbit S, Trope W, Konsker H, Fatodu E, Berry MS, Poulstides G, Norton J, Burdon T, Backhus L, Cooke R, Tang H. Rationale and design of a mechanistic clinical trial of JAK inhibition to prevent ventilator-induced diaphragm dysfunction. Respir Med. 2021 Nov-Dec;189:106620. doi: 10.1016/j.rmed.2021.106620. Epub 2021 Sep 21. | |
| 39122555 | Background | Shrager JB, Randle R, Lee M, Ahmed SS, Trope W, Lui N, Poultsides G, Liou D, Visser B, Norton JA, Nesbit SM, He H, Kapula N, Wallen B, Fatodu E, Sadeghi CA, Konsker HB, Elliott I, Guenthart B, Backhus L, Cooke R, Berry M, Tang H. JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle. Life Sci Alliance. 2024 Aug 9;7(11):e202402885. doi: 10.26508/lsa.202402885. Print 2024 Nov. |
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No plan to share IPD.
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| ID | Term |
|---|---|
| C479163 | tofacitinib |
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| Placebo to match Tofacitinib | Drug | administered twice daily for two days |
|
| Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition. | Compare differences in muscle between the drug-treated and placebo groups in proteolytic pathways (quantitative PCR for atrogein, MuRF1, and FoxO gene expression, western blot analysis for protein levels of these and protein polyubiquitination, proteasomal activity, qPCR and western blots for expression of LC3). | 4-6 years |
| Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition. | Compare differences in muscle between the drug-treated and placebo groups in transcriptomic gene profiling, and metabolomic profiling.. | 4-6 years |