Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction

Diaphragm Injury Clinical Trial

Official title:

A Clinical Trial of JAK Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03681275
• Other study ID #: IRB-47826
• Secondary ID: 3R01AG069858-02W
• Status: Recruiting
• Phase: Phase 2
• Start date: September 3, 2019
• Est. completion date: November 16, 2024

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: November 16, 2024
• Est. primary completion date: November 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients undergoing esophagectomy

Exclusion Criteria:

• Patients with more than mild pulmonary dysfunction
• Patients with any neuromuscular disease that might compromise diaphragm function
• Patients with abnormal liver or kidney function
• Patients taking any immunosuppressant medication (including prednisone) or antifungal medications
• History of tuberculosis
• Weight loss of >5% of body weight over previous 6 months
• Pregnancy

Related Conditions & MeSH terms

• Diaphragm Injury

Intervention

Drug:
• Tofacitinib 10 MG [Xeljanz]
administered twice daily for two days
• Placebo to match Tofacitinib
administered twice daily for two days

Locations

Country	Name	City	State
United States	Stanford University Medical Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Secondary	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