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Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate–severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial

The American Journal of Gastroenterologyvolume 113pages15161523 (2018) | Download Citation

Subjects

Abstract

BACKGROUND

Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization.

METHODS

The study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate–severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0–1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization.

RESULTS

A significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04). HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were no serious adverse events.

CONCLUSION

In this small, proof-of-concept, phase 2A trial, the use of HBOT as an adjunctive therapy to steroids for UC patients hospitalized for moderate–severe flares resulted in higher rates of clinical remission, and a reduction in rates of progression to second-line therapy during the hospitalization. Larger well-powered trials are needed, however, to provided definitive evidence of therapeutic benefit.

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Author information

Affiliations

  1. University of California at San Diego, La Jolla, CA, USA

    • Parambir S. Dulai MD
    • , Christella E. Widjaja PhD
    •  & John T. Chang MD
  2. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

    • Parambir S. Dulai MD
    • , Jay C. Buckey Jr. MD
    • , Judy A. Ptak RN, MSN
    • , Michael W. Gleeson MD, PhD
    • , Jeffery M. Adler MD
    • , Nihal Patel MD
    • , Laurie A. Skinner
    • , Kimberly D. Thompson MS
    •  & Corey A. Siegel MD, MS
  3. Mayo Clinic, Rochester, MN, USA

    • Laura E. Raffals MD
    • , Paul L. Claus MD
    •  & Shawn P. Haren
  4. University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    • Jason M. Swoger MD
    • , Kevin O’Toole MD
    •  & Kimberly Goldby-Reffner

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Guarantor of the article

Parambir S. Dulai, MD.

Specific author contributions

Study design: PSD and CAS. Patient recruitment: PSD, LER, JMS, MWG, JMA, NP, LAS, SPH, KGR, CAS. Hyperbaric treatment: PSD, JCB, PLC, KT, JAP, MWG. Data analysis: PSD, JCB, CEW, KDT, JTC, CAS. Study supervision: PSD and CAS. Manuscript draft and critical revisions: PSD, JCB, LER, JMS, PLC, KT, CAS. Final approval of manuscript: all authors.

Financial support

This study was funded by the Foundation for Clinical Research in IBD and the Broad Medical Research Program at the Crohn’s and Colitis Foundation of America. PSD is supported by the NIDDK training grant 5T32DK007202.

Potential competing interests

PSD has received research support from Takeda and Pfizer. JMS has received research support from Abbvie. CAS has served as a consultant for Abbvie, Amgen, Lilly, Janssen, Sandoz, Pfizer, Prometheus, Takeda, and UCB, and has received lecture fees from Abbvie, Janssen, Pfizer, and Takeda. The remaining authors have no conflicts of interest.

Corresponding author

Correspondence to Parambir S. Dulai MD.

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DOI

https://doi.org/10.1038/s41395-018-0005-z