Study to Determine if Hyperbaric Oxygen Therapy is Helpful for Treating Radiation Tissue Injuries
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 Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Queensland
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Brisbane, Queensland, Australia, 4064
- Wesley Medical Center
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Tasmania
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Hobart, Tasmania, Australia, 7001
- Royal Hobart Hospital
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Mexico City, Mexico, 14080
- Instituto Nacional de Cancerologica
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Cape Town, South Africa
- University of Stellenbosch
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Pretoria, South Africa, 0001
- University of Pretoria Medical Center
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Istanbul, Turkey, 34390
- Istanbul University Medical Center
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South Carolina
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Columbia, South Carolina, United States, 29203
- Palmetto Health Richland
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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ACTIVE_COMPARATOR: A
Hyperbaric Oxygen Therapy
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HBO at 2.0 ATA
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SHAM_COMPARATOR: B
Normal Air
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Normal air under pressure (1.1 ATA)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
SOMA (Subjective, Objective, Management, Analytic) scale used to determine late effects to normal tissue (LENT) score
Time Frame: pre-treatment, post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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pre-treatment, post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Clinical assessment using one of the following criteria:
Time Frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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Healed
Time Frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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Modestly improved (< 50% lesion resolution)
Time Frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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Not improved
Time Frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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Other (e.g. lesion recurrence, lesion size progression)
Time Frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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Significant Improvement (>50% lesion resolution)
Time Frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Dick Clarke, CHT, National Baromedical Services
Publications and helpful links
General Publications
- Curi MM, Dib LL. Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg. 1997 Jun;55(6):540-4; discussion 545-6. doi: 10.1016/s0278-2391(97)90478-x.
- Joseph DL, Shumrick DL. Risks of head and neck surgery in previously irradiated patients. Arch Otolaryngol. 1973 May;97(5):381-4. doi: 10.1001/archotol.1973.00780010393005. No abstract available.
- Samuels L, Granick MS, Ramasastry S, Solomon MP, Hurwitz D. Reconstruction of radiation-induced chest wall lesions. Ann Plast Surg. 1993 Nov;31(5):399-405. doi: 10.1097/00000637-199311000-00003.
- Hart GB, Mainous EG. The treatment of radiation necrosis with hyperbaric oxygen (OHP). Cancer. 1976 Jun;37(6):2580-5. doi: 10.1002/1097-0142(197606)37:63.0.co;2-h.
- Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983 May;41(5):283-8. doi: 10.1016/0278-2391(83)90294-x.
- Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg. 1983 Jun;41(6):351-7. doi: 10.1016/s0278-2391(83)80005-6. No abstract available.
- Bevers RF, Bakker DJ, Kurth KH. Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Lancet. 1995 Sep 23;346(8978):803-5. doi: 10.1016/s0140-6736(95)91620-2.
- Woo TC, Joseph D, Oxer H. Hyperbaric oxygen treatment for radiation proctitis. Int J Radiat Oncol Biol Phys. 1997 Jun 1;38(3):619-22. doi: 10.1016/s0360-3016(97)00017-5.
- Williams JA Jr, Clarke D, Dennis WA, Dennis EJ 3rd, Smith ST. The treatment of pelvic soft tissue radiation necrosis with hyperbaric oxygen. Am J Obstet Gynecol. 1992 Aug;167(2):412-5; discussion 415-6. doi: 10.1016/s0002-9378(11)91421-5.
- Feldmeier JJ, Heimbach RD, Davolt DA, Brakora MJ. Hyperbaric oxygen as an adjunctive treatment for severe laryngeal necrosis: a report of nine consecutive cases. Undersea Hyperb Med. 1993 Dec;20(4):329-35.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Project HORTIS
- ISRCTN85456814
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