Official Title: “Hyperbaric Oxygen Radiation Tissue Injury Study - Project HORTIS”

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.)

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study

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.

Primary:

• 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 No

Secondary:

• 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 No
• Healed post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years No
• 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 No
• Not improved post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years No
• 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 No
• 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 No

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.

Lead Sponsor: Baromedical Research Foundation

Palmetto Health Richland

Columbia South Carolina 29203 United States

Wesley Medical Center

Brisbane Queensland 4064 Australia

Royal Hobart Hospital

Hobart Tasmania 7001 Australia

Instituto Nacional De Cancerologica

Mexico City  14080 Mexico

University of Pretoria Medical Center

Pretoria  0001 South Africa

Istanbul University Medical Center

Istanbul  34390 Turkey

Overall Clinical Trial Officials and Contacts

Dick Clarke, CHT Principal Investigator Baromedical Research Foundation  

Overall Contact: Dick Clarke, CHT 803-434-7101 dick.clarke@palmettohealth.org

Information obtained from ClinicalTrials.gov on July 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00134628

Study ID Number: Project HORTIS

ClinicalTrials.gov Identifier: NCT00134628

Health Authority: United States: Institutional Review Board

Research activities undertaken by the Baromedical Research Foundation