Evaluation of Hyperbaric Oxygen Therapy as an Adjunct to Biologic Therapy in Moderate to Severe Ulcerative Colitis: A Randomized Controlled Trial

The primary objective of this study is to compare the **effectiveness** of biological treatment alone (group I, standard treatment) with a combined treatment regimen that includes biological treatment and **hyperbaric oxygen therapy** (group II, combined treatment) in adults with moderate to severe **ulcerative colitis**. This comparison is clinically relevant as it aims to determine whether the addition of hyperbaric oxygen therapy can enhance the therapeutic outcomes of standard biological treatments, potentially offering a more effective management strategy for this chronic inflammatory bowel disease.

Secondary objectives include the assessment of the effectiveness of biological treatment alone versus the combined treatment after 14 weeks and 12 months following the initial dose. This evaluation will provide insights into the long-term benefits and sustainability of the combined treatment approach, which is crucial for optimizing patient care and improving quality of life in individuals affected by ulcerative colitis.

The clinical trial focuses on patients diagnosed with **ulcerative colitis**, specifically targeting individuals aged 18 to 70 years. The study population includes both male and female participants, with no vulnerable populations selected. Participants are required to have a moderate or severe form of the disease, as indicated by a Mayo scale score of at least 6 points, with at least 2 points attributed to endoscopy. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection criteria emphasize a histopathologically confirmed diagnosis of ulcerative colitis for a minimum of three months. Additionally, patients with a history of the disease for eight years or more must have undergone a colonoscopy within the last year to check for dysplasia. The trial includes individuals who have shown a lack of response to steroid treatment, defined as either steroid resistance or dependence, or those who have not responded to azathioprine or mercaptopurine treatment. Participants are also those qualified for treatment with infliximab, vedolizumab, or ustekinumab. Lifestyle factors such as diet and physical activity are not specified in the trial data.

The clinical trial is designed to evaluate the efficacy and safety of **hyperbaric oxygen therapy** as an adjuvant treatment compared to biologic therapy alone in adults with moderate to severe **ulcerative colitis**. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to span a duration of approximately three years, with an estimated end date in June 2027. Participants will be involved in the study for a maximum treatment period of 12 months.

The sequence of study visits includes an initial screening visit to confirm eligibility based on specific inclusion criteria, such as a Mayo scale score of at least 6 points and a histopathologically confirmed diagnosis of ulcerative colitis for at least three months. Following the screening, participants will be randomized into two groups: one receiving standard biological treatment and the other receiving a combination of biological treatment and hyperbaric oxygen therapy. Follow-up visits will occur at regular intervals to monitor the clinical response and safety of the treatments. The primary endpoint is the percentage of clinical remission after 12 months, defined as the complete resolution of clinical symptoms and endoscopic markers of mucosal inflammation. Secondary endpoints include the assessment of clinical response rates at 14 weeks and 12 months.

The end-of-study visit will occur after the 12-month treatment period, where final assessments will be conducted to evaluate the long-term effects of the treatments. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or choose to withdraw consent. The trial aims to provide comprehensive data on the comparative effectiveness of the treatment regimens, contributing valuable insights into the management of ulcerative colitis.

The clinical trial involves the use of several treatments, including both experimental and non-experimental medications. **STELARA 130 mg** concentrate for solution for infusion is an experimental medication used in this study. It contains the active substance **ustekinumab**, a protein-based therapeutic agent. The pharmaceutical form is a concentrate for solution for infusion, administered via **intravenous infusion**. The maximum daily dose is 520 mg, with a total treatment period of up to 12 months. The medication is provided by Janssen-Cilag International NV.

Another formulation of **STELARA** used in the trial is the 90 mg solution for injection in a pre-filled pen. This formulation also contains **ustekinumab** and is administered through **intravenous infusion**. The maximum daily dose is 90 mg, with a treatment duration of up to 12 months. This product is also supplied by Janssen-Cilag International NV.

**Entyvio 300 mg** powder for concentrate for solution for infusion is included as a comparator treatment. It contains the active substance **vedolizumab**, another protein-based therapeutic agent. The pharmaceutical form is a solution for infusion, administered via **intravenous use**. The maximum daily dose is 300 mg, with a treatment period of up to 12 months. This product is provided by Takeda Pharma A/S.

**Zessly 100 mg** powder for concentrate for solution for infusion is also used as a comparator. It contains **infliximab**, a protein-based therapeutic agent. The pharmaceutical form is a solution for infusion, administered via **intravenous use**. The dosing is based on body weight, with a maximum daily dose of 5 mg/kg, and the treatment period extends up to 12 months. This product is supplied by Sandoz GmbH.

**TLEN MEDYCZNY Linde gaz** is used as a non-experimental treatment in the study. It contains **oxygen** as the active substance, provided in the form of medicinal gas, compressed. The administration route is **inhalation**, with a maximum daily dose of 100% oxygen. The treatment period is up to 6 months. This product is provided by Linde Gaz Polska Sp. z o.o.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the treatment protocols. The study aims to evaluate the efficacy and safety of these treatments in adults with moderate to severe **ulcerative colitis**.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of moderate to severe **ulcerative colitis**. The primary endpoint is the percentage of clinical remission after 12 months of treatment. This is defined as the percentage of patients who achieve complete resolution of clinical symptoms, such as diarrhea and blood in the stool, as well as the resolution of endoscopic markers of mucosal inflammation.

Secondary endpoints include the assessment of the clinical response rate in patients receiving combination therapy compared to those receiving biological therapy alone. This will be evaluated at two timepoints: 14 weeks and 12 months after the administration of the first dose of the biological drug. Additionally, the percentage of complete clinical remission in the group receiving combined treatment versus the group receiving biological treatment alone will be assessed 14 weeks after the first dose.

The trial will involve the use of biological treatments such as infliximab, vedolizumab, and ustekinumab, alongside hyperbaric oxygen therapy as an adjuvant treatment. The efficacy parameters will be collected and analyzed at specified intervals to determine the effectiveness of the combined treatment approach compared to standard biological therapy alone.