Study to Determine if Hyperbaric Oxygen Therapy is Helpful for Treating Radiation Tissue Injuries

Phase 3

Terminated

• Conditions: Radiation Injuries

• Registration Number: NCT00134628
• Lead Sponsor: National Baromedical Services

Brief Summary

The principle objective of this research is to more precisely determine the degree of benefit that hyperbaric oxygen therapy affords in the treatment of late radiation tissue injury.

The study has eight\* components. Seven involve the evaluation of established radionecrosis at varying anatomic sites (mandible, larynx, skin, bladder, rectum, colon, and gyn). The eighth will investigate the potential of hyperbaric oxygen (HBO) therapy to prophylax against late radiation tissue injury.

\*(One of the arms, HORTIS IV - Proctitis has been closed to further patient recruitment. This decision was based on an interim statistical analysis which generated sufficient evidence to support closing down this arm of HORTIS.)

Detailed Description

Radiation therapy is a key component of the control and eradication of malignant disease. Adequate tumoricidal doses may, however, result in damage to surrounding healthy tissue. Therapeutic radiation injuries to non-target tissues can be divided into acute, sub-acute, and delayed complications. Acute injuries are considered a direct cellular toxicity, self-limiting, and in most cases successfully managed symptomatically. Sub-acute injuries are typically identifiable in only a few organ systems, e.g., radiation pneumonitis. These, too, are generally limited but occasionally evolve to late complications. Late changes occur several months to many years after completing radiotherapy.

The etiology of radiation's late effects to normal tissue (LENT) varies somewhat between organ systems. Its hallmark, however, is one of culminating in an obliterative endarteritis, and local hypoxia.

The incidence of LENT is related to both total radiation exposure and the length of time a patient is out from completing radiotherapy. The higher the dose, the longer the interval from exposure, the greater the risk. In many cases, resulting radionecrotic lesions seriously impair form and function, and require extensive surgical correction or repair. Such surgery is fraught with complications, hence the inclusion of a "prophylactic" hyperbaric oxygen arm. A disturbing degree of mortality further complicates the development of LENT.

Hyperbaric oxygen has been utilized in the treatment of radiation tissue injury for several decades. Most of the supportive basic science and clinical evidence stems from the management of mandibular osteoradionecrosis. More recently, the use of hyperbaric oxygen has been extended to other anatomic sites. This expanded use is based, in large part, on a presumed common underlying pathophysiology of LENT, regardless of its anatomic location. Supportive clinical evidence for these other sites is limited, however, and in need of a greater degree of scientific scrutiny.

Study Timeline

• Study Start: 2001-01
• Study First Submitted: 2005-08-23
• Study First Submitted QC: 2005-08-24
• Study First Posted: 2005-08-25
• Primary Completion: 2011-08
• Status Verified: 2012-02
• Study Completion: 2015-12
• Last Update Submitted: 2016-01-11
• Last Update Posted: 2016-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 248

Inclusion Criteria

• Endarteritis
• Hypovascularity
• Diarrhea
• Cramping
• Obstruction
• Stricture
• Pain
• Hemorrhage
• Wall Changes
• Ulceration
• Hypocellularity
• Mucosal thickening
• Vomiting
• Tenesmus
• Constipation
• Perforation
• Fistula
• Obstipation
• Tissue hypoxia

Exclusion Criteria

• Pregnancy
• Reactive airway disease
• Radiographic evidence of pulmonary blebs or bullae
• Untreated pneumothorax
• Previously documented ejection fraction less than 35%
• History of seizures except childhood febrile seizures
• Cardiovascular instability
• Mechanical ventilator support with the exception of those patients who are immediately (1-5 days) post-operative
• Unable to follow simple commands
• Not orientated to person, place, time
• Participating as a subject in any other medical or biomedical research project; if previously involved as a subject, sufficient time must have elapsed to permit "wash out" of any investigational agent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
SOMA (Subjective, Objective, Management, Analytic) scale used to determine late effects to normal tissue (LENT) score	pre-treatment, post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years

Secondary Outcome Measures

Name	Time	Method
Healed	post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Significant Improvement (>50% lesion resolution)	post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Clinical assessment using one of the following criteria:	post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Modestly improved (< 50% lesion resolution)	post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Not improved	post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Other (e.g. lesion recurrence, lesion size progression)	post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years

Trial Locations

Locations (7)

Palmetto Health Richland; 🇺🇸 Columbia, South Carolina, United States

Wesley Medical Center; 🇦🇺 Brisbane, Queensland, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Instituto Nacional de Cancerologica; 🇲🇽 Mexico City, Mexico

University of Stellenbosch; 🇿🇦 Cape Town, South Africa

University of Pretoria Medical Center; 🇿🇦 Pretoria, South Africa

Istanbul University Medical Center; 🇹🇷 Istanbul, Turkey