Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction

NCT03681275 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB-478263R01AG069858-02W1
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Diaphragm Injury

Keywords

Ventilator-induced Diaphragm Dysfunction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Increase in muscle strength due to JAK inhibition

  4-5 years

Other Outcomes (3)

• Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition.

  4-6 years

• Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition.

  4-6 years

• Exploratory: Determine mechanisms of changes in muscle strength and ventilator-induced diaphragm dysfunction by JAK inhibition.

  4-6 years

Study Arms (2)

Tofacitinib

EXPERIMENTAL

Patient will receive two days treatment with tofacitinib prior to the surgery.

Drug: Tofacitinib 10 MG [Xeljanz]

Placebo

PLACEBO COMPARATOR

Patient will receive two days treatment with placebo prior to the surgery.

Drug: Placebo to match Tofacitinib

Interventions

Tofacitinib 10 MG [Xeljanz] DRUG

administered twice daily for two days

Also known as: XELJANZ

Tofacitinib

Placebo to match Tofacitinib DRUG

administered twice daily for two days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing esophagectomy

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Stanford University Medical Center

Stanford, California, 94305, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 34655959 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.

  PMID: 39122555 BACKGROUND

MeSH Terms

Interventions

tofacitinib

Study Officials

• Joseph Shrager, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cheyenne A Clinical Research Coordinator, B.S, M.S

CONTACT

3107201689; csadeghi@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 24, 2018
• Study Start: September 3, 2019
• Primary Completion: November 30, 2025
• Study Completion (Estimated): November 30, 2026
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)