Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03100175 |
| Other study ID # |
113-17 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
March 6, 2017 |
| Last updated |
March 28, 2017 |
| Start date |
May 1, 2017 |
| Est. completion date |
March 15, 2019 |
Study information
| Verified date |
March 2017 |
| Source |
Rabin Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Frailty, one of geriatric syndromes, is considered a major obstacle for recovery from
physiological stress. Such stress is imposed on patients with cancer by virtue of the
disease itself but even more so by the treatment. Moreover, malignancy and chemotherapy both
cause accelerated loss of muscle mass, deconditioning, frailty and negative outcomes.
Several studies showed that chemotherapy accelerates ageing.
Muscle mass reserve was found to be a major predictor of outcomes in patients treated with
chemotherapy. Recently, several studies suggest that active muscle strength training during
chemotherapy may decrease side effects, improves the ability to deliver intended doses of
treatment and may even affect oncological outcomes.
In the proposed study we intend to assess the contribution of physical training to the
well-being of chemotherapy treated older patients, assessed by molecular and physiological
parameters.
We intend to recruit lymphoma patients above age of 70 and prospectively and randomly assign
them to the intervention group (strength, aerobic and balance training during the
chemotherapy) and control group (standard care with no special emphasis on physical activity
during the treatment).
We will measure clinical outcomes such as treatment tolerance and effects as well as
physiological outcomes (muscle strength and mass, elements activities of daily living) and
laboratory markers of ageing such as DNA methylation, INK 4a expression, telomere length and
serum levels of inteleukin 6, CRP among others.
Our hypothesis is that physical training will improve patients' ability to complete the
treatment with fewer side effects, will provide them with better daily functioning and
better muscle strength/function. We also hypothesize that the ageing process, as shown by
laboratory senescence markers, will be attenuated in the intervention group.
Description:
Introduction Rising life expectancy and an exponential correlation between age and cancer
incidence brought about a new field of geriatric oncology. As patients above age 65 account
for more than 60% of cancer diagnoses with octogenarians and even nonagenarians being not
rare in oncology practice, a geriatric prospective becomes essential in the treatment
process.
Frailty, a nebulous term, defined on the metabolic basis as "vicious circle of energetic
dysregulation", is largely heterogeneous in younger elderly population, with some people
being frail, others borderline -"prefrail" or even non-frail - "fit". Nevertheless, frailty
becomes universal as senescence progresses, as it is tightly linked with physiological
ageing and usually worsened by comorbidities. Elderly patients can seem fit and in good
health but still be "sub-clinically" frail. The clinical significance is a gradual loss of
ability to cope and recover from physiological stress.
Oncological patients are exposed to two major physiological stresses: the catabolic state
induced by the disease and the chemotherapy challenge to tissues.
Curative-intent chemotherapy is usually withheld from very frail individuals but elderly
patients deemed to be pre-frail or fit are frequently treated according to standard or
mildly modified protocols, putting them at risk of slow or no recovery from drug related
toxicity. Moreover, it was shown in other studies that chemotherapy itself accelerates
senescence by stress related mechanisms and promotes muscle loss and frailty in younger
individuals .
Numerous tools have been developed to try to measure frailty and help treatment decisions.
Despite some differences, the main bulk of evaluated elements in all of those tools refer in
some way to patient's ability to perform physical activity including muscle strength,
walking speed, level of energy production and feeling tired, emphasizing the critical role
of muscles in elderly general condition .
Interventions shown to prevent deterioration and even improve physical condition of frail
individuals were muscle training and nutritional support.
On the other hand, incorporation of physical training in younger oncological patients was
shown to improve outcomes such as ability to complete chemotherapy without dose adjustment,
subjective feeling of less fatigue, better daily functioning, earlier return to work and
better physical measures of muscle strength and cardio-pulmonary fitness.
The positive impact of physical activity on both: preventing of frailty deterioration and
ability to withstand chemotherapy better, led us to hypothesis that it would be especially
beneficial in elderly cancer patients. The benefit would probably expand beyond the clinical
and functional measures and would be also expressed on the molecular level with reduced
levels of senescence markers.
We intend to prospectively recruit lymphoma patients above age of 70, admitted to Davidoff
Cancer Center outpatient clinic and being judged eligible for chemotherapy at 75% of more of
full dose. The patients will be randomly assigned to an intervention or control group. All
patients will undergo a similar evaluation at the beginning and after completion of
chemotherapy.
Standard evaluation of all patients:
- anthropomorphic measures (hand grip by a hand-held dynamometer and quadriceps strength
by a sitting tensiometer), and functional measures (gait speed by 6 minute-walk,
sit-to-stand test, functional reach and timed get-up-and-go test) - performed by a
physiotherapist at the day of recruitment and one to two months after chemotherapy
completion
- muscle mass according to muscle mass index calculation from the cross section area of
both psoas muscles at the level of L3 vertebra corrected to height; and body
composition according to mean Housfield units of the psoas section area - done by the
study physician, using CT scans at the begging and after the treatment
- functional, nutritional and cognitive function as performed routinely at the Senior
Oncology Program at Davidoff Cancer Center - done at the beginning and after the
treatment by a team member
- standard blood tests including hemoglobin, white blood cells, albumin, CRP to be drawn
before and after the treatment
- markers of senescence to be measured after the treatment completion: DNA methylation at
three selected loci, expression of p16INK4A , telomere length and plasma levels of IL-6
and CRP - markers of "inflamm-aging" - a process of chronic low-level inflammation
universal in older individuals.
- After the standard part of the evaluation by a physiotherapist, the patient will be
scheduled for another appointment and taught a set of exercises including strength
training for upper and lower limbs (with elastic bands and weights, rising up from
chair and climbing stairs), fitness work out (brisk walking) and balance exercises, as
recommended by senior sport programs.
- Patients will be provided with printed instructions explaining the recommended
exercises, and with a diary to fill in, with days and number of repetitions of specific
training elements to be checked in according to their compliance. Patients will also be
equipped with a pedometer and will be asked to record the counts regularly
- Patients will be met again by a physiotherapist for follow up at the start of every
chemotherapy course (once in 3-4 weeks) and will be contacted by phone twice weekly to
assure they stick to the training recommendations The control group will receive
standard treatment and follow-up with no special emphasis on physical activity.
The size of each group will be about 50 patients. Innovation To the best of our knowledge,
there are no prospective studies published on this kind of intervention in elderly cancer
patients. Home-based physical training is a simple, low-cost modality, which, if proven
effective, would appreciably improve patient-related outcomes and probably reduce short and
long-term costs of patient care. There are no studies that explored differences in cellular
senescence in elderly cancer patient undergoing physical training.
Study design This will be a prospective randomized study, with an intervention to which no
blinding can be done. The cross-sectional comparisons between the groups and longitudinal
changes will be searched.
Statistics The statistical analysis of the data will be performed by a statistician of Rabin
Medical Center using SPSS software and according to accepted standards.
