Secondary Lymphedema Clinical Trial
Official title:
Hyperbaric Oxygen Therapy to Reduce Lymphedema After Breast Cancer -an Explorative Clinical Trial
The purpose of this study is to examine if pressurechamber treatment (HBOT) can reduce early stages of breast cancer related lymphedema, and to explore the mechanisms involved in the disease progress.
Lymphedema (LE) is a potential complication of primary breast cancer treatment and the
influence of LE on the quality of life is well-established. To date there is no established
treatment that can reverse lymphedema. Patients are dependent on compression garments and
manual lymphatic drainage to prevent progression of LE and worsening of discomfort, pain,
upper limb dysfunction/sensation, skin problems and infections.
As a development in treatment of tissue damage after radiation treatment HBOT is used in the
treatment of radiation induced mandibular necrosis, hemorrhagic cystitis or proctitis
following pelvic radiation. The pathology, which correlates to the effect of HBOT include
neovascularization, as well as organization and reduction in fibrous tissue, and new evidence
also shows an increase in the number of lymphatic vessels in irradiated oral mucosa. Some
studies have found that HBOT might also reduce arm edema in breast cancer patients, but
evidence is inconsistent and mainly based on chronic and long existing lymphedema in long
term BC survivors. The investigators argue that the possibility of remodeling of mature
fibrotic tissue is less pronounced when the lymphedema has been present over prolonged
periods of years, limiting the possibility of treatment success. Although HBOT is a lengthy
and time-consuming treatment, it is documented safe in all aspects with little risk of side
effects, and the potential health gains from the treatment are immense.
This explorative HBOT trial was designed to generate hypotheses about the conditions under
which HBOT is effective to reduce lymphedema, and to reveal new aspects of the role of tissue
composition on the effectiveness of HBOT. The early initiation of HBOT is the key factor in
this set up, which is different from the previous studies in the field. To be able to do so,
all participants in a randomized controlled exercise trial (LYCA), who develop lymphedema
during the first year after surgery will be invited to participate in the HBOT trial.
This trial was accepted with regards to the experimental use of medical oxygen in a pressure
chamber for the treatment of lymphedema in the National Health and Medicines Authority in
2015; protocol number R96- A6604-14- S22, EUDRACT no: 2015-000604-25.
Aims and hypothesis The primary aim in this explorative trial is to examine whether HBOT is
effective in treating early LE. Secondly, the aim is to examine the importance of the
conditions under which HBOT is more effective in treating LE. Effects of HBOT (primary
endpoints) will be evaluated as objective measurements of the affected and contralateral arm
volume assessed by DXA scan and Light perometry. Changes in lymphatic clearance rate before
and after HBOT (secondary endpoint) will be measured by lymphoscintigraphy and biomarkers of
inflammation and collagen levels in blood samples. Other secondary endpoints are patient
reported outcomes of symptoms of lymphedema, physical and psychological function, fatigue,
and quality of life, and will be assessed by questionnaire.
It is hypothesized that HBOT will reduce the volume and symptoms of persistent LE in the
patients receiving this treatment, to a clinically non-significant level. Furthermore, it is
hypothesized that HBOT cause reduced patient reported symptoms of lymphedema and fatigue and
increased physical and psychological function and quality of life.
Method
The LYCA HBOT trial is an explorative and observational study, offering all participants in
the exercise trial, who develop lymphedema, a treatment course with HBOT. In addition, an
equal number of matched control subjects without lymphedema from the exercise trial will be
included for blood sampling and DXA scans. It is planned to start in September 2016 and to be
ended with the last follow up (6 months) of the last participant, in May 2018. Patients are
invited at 12 months follow-up in the LYCA exercise trial if they present with the following
criteria for lymphedema persisting more than 4 weeks:
- a swelling of the arm on the operated side, corresponding to >3% increase in inter limb
volume change from the baseline measurement
- a score of 2 points or more on numeric rating scale for self reported swelling,
heaviness and tightness
- a clinical exam where 2 or more of the following 4 criteria must be present (i-iii are
compared with the unaffected side): i) decreased visibility of subcutaneous veins on the
ventral lower arm or dorsal hand ii) loss of normal contours in the region of the medial
side of the elbow/distal end of the upper arm iii) thicker skin and subcutis on
palpation iv) pitting edema
The HBOT component:
HBOT includes compression to 2.4 Bar (ATA) in a multi-place hyperbaric chamber at
Rigshospitalet. Patients breathe 100% oxygen via a transparent hood for a total of 100
minutes including two 5-minutes periods of de- and ascent. The course of treatment comprises
a total of 40 pressure exposures, distributed as 5 days a week for 8 continuous weeks. The
women will be encouraged to continue exercising 3 times a week throughout the treatment
period, adherence to exercise promoted by mobile phone text messages.
Analysis For this explorative trial, no power calculation is carried out, due to the
explorative focus to generate hypotheses. Descriptive statistics will be used to look at
possible tendencies, associations and differences. Arm volume over time will be compared, and
limb volume difference in those women who have carried out the progressive resistance
training compared to the women who received the usual care control condition will be
evaluated. Furthermore, the possible association between effect of HBOT and amount of
exercise will be examined, as will the increase in or level of muscle strength, symptom
burden, body composition, physical function, and health related quality of life.
In analysis of blood samples of HBOT participants and control subjects, levels of the
biomarkers in question will be compared and contrasted, both at baseline (before HBOT) and in
changes over time (during and after HBOT). Within the groups of controls and HBOT
participants, there are individuals from each LYCA-exercise intervention arm.
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