Clinical trial NCT03681275: Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction
Official title: A Clinical Trial of JAK Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diaphragm Injury
Keywords: Ventilator-induced Diaphragm Dysfunction
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-09-24
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Prevention of ventilator-induced diaphragm dysfunction by JAK inhibition
timeFrame: 5-6 years
Secondary outcomes:
measure: Increase in muscle strength due to JAK inhibition
timeFrame: 4-5 years
Other outcomes:
measure: Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition.
timeFrame: 4-6 years
measure: Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition.
timeFrame: 4-6 years
measure: Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition.
timeFrame: 4-6 years
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Stanford University
name: Joseph Shrager, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.