Introduction

Hyperbaric oxygen therapy (HBOT) is a treatment that delivers 100% oxygen in a pressurized chamber. HBOT enhances tissue oxygenation and neovascularization and proved clinical efficacy in chronic wounds, post-radiation proctitis and enteritis, perianal fistulizing Crohn’s disease, and acute severe ulcerative colitis. Refractory ulcerative colitis (UC) remains a major therapeutic challenge.

Aims & Methods

We evaluated the tolerability, preliminary efficacy, and mechanistic effects including perfusion kinetics measured with intestinal ultrasound (IUS) of 10 and 20 sessions of HBOT in patients with UC. PARADOX was an investigator-initiated, prospective, open label, uncontrolled, dose-finding pilot trial (phase 2a) in biologic-experienced patients with moderate-to-severe, highly refractory UC with a follow-up of 26 weeks (Mayo score >5, MES ≥2, failed ≥2 classes advanced therapies). Patients (n=16; 8 per arm) continued optimized, stable dose background therapy and received 10 or 20 sessions HBOT (2.4 ATA, 120 minutes per day with two 5-minute air breaks). The primary efficacy outcome was predefined composite clinical and endoscopic response (3-point and 30% decrease in Mayo score, RB = 0 and 1-point decrease in MES) at week (W) 12. Other outcomes included tolerability; clinical, symptomatic, endoscopic, and biochemical response, and transmural response assessed by IUS including contrast-enhanced ultrasound (CEUS) to evaluate bowel wall thickness (BWT), vascularity and perfusion kinetics. Endoscopy and IUS were centrally read and adjudicated.

Results

Baseline characteristics were comparable in both cohorts with median age: 48 vs 64 years; disease duration: 12 vs 9 years; ≥4 prior advanced therapies: 3/8 in both; Mayo score: 10.5 vs 9.
At W12, the predefined composite clinical and endoscopic response rate was met in 2/8 patients with 10 sessions and 4/8 patients with 20 sessions. Clinical, endoscopic, symptomatic, biochemical, and IUS parameters all improved over time in both HBOT cohorts with a trend towards larger improvement after 20 compared to 10 sessions (See Table).
At W12, clinical responders demonstrated a significant increase in peak enhancement on CEUS compared to baseline (12.1 dB, 95% CI: 0.8 to 34.3), while non-responders showed a numerical decrease (–5.4 dB, 95% CI: –20.9 to 4.0). This divergent trajectory was consistent across perfusion parameters related to both wash-in and wash-out (e.g., time to peak, wash-in and wash-out rate, area under the curve), suggesting a treatment-related vascular response. In contrast, early gains in non-responders had waned by W12. This effect was numerically larger after 20 sessions, supporting a potential dose–response effect.
HBOT was well tolerated with no dose-limiting toxicities.

Conclusion

HBOT is a feasible adjunctive therapy in treatment-refractory moderate-severe UC. CEUS showed improved intestinal perfusion in HBOT responders, which offers promising non-invasive tools for response assessment. These findings provide a rationale for a randomized dose-optimized phase 2 trial with potentially longer duration of treatment.

Introduction

Few studies have evaluated the efficacy of butyric acid in treating children with inflammatory bowel disease (IBD).

Aims & Methods

In children and adolescents with recently diagnosed IBD, the purpose of this research was to assess the efficacy of oral sodium butyrate as an adjunct to conventional treatment.This trial was unicentric, prospective, randomised, and placebo controlled. 150 mg sodium butyrate single dose (group A) or a placebo (group B) were randomly assigned to patients with ulcerative colitis or Crohn's disease aged 7–18 years who were receiving conventional medication based on the severity of their conditions. Disease activity, C-reactive protein (CRP), and faecal calprotectin concentration differences between the two study groups at 12 weeks of the trial were the main outcomes.

Results

With 44 patients in group A and 44 in group B, 88 individuals with initially active illness finished the research. Most patients experienced remission by week 12 of the study (36 patients in Group A with sodium butyrate-82%, and 11 patients in Group B with placebo-48%). Between the two groups, a significant difference in disease activity was seen (p = 0.001), with a signifigant higher percent of cases in remission among those from lot A that received sodium butirate compared to placebo. The sodium butyrate group appeared to have less systemic inflammation than the other group, as evidenced by the significantly lower CRP levels in Group A (18.14 ± 11.19 mg/L) compared to Group B (57.00 ± 33.28 mg/L) at 12 weeks (T2) (P < 0.001). No negative effects were recorded by any of the patients. Fecal calprotectin in Group A dropped much more after 12 weeks (T2) (P < 0.001), suggesting that the sodium butyrate group was better able to regulate intestinal inflammation.

Conclusion

In newly diagnosed children and adolescents with IBD, a 12-week sodium butyrate supplementation did demonstrate effectiveness as an additional treatment and decreased the rate of relapsing cases.

Disclosure

Nothing to disclose