Osteoporosis in Post-menopausal Women Clinical Trial
Official title:
Multicentered, Randomized Study of Safety and Efficacy of Whole-body Vibration as add-on to Standard Pharmacological Treatment of Osteoporosis in Post-menopausal Women
Multicentered, randomized study of safety and efficacy of whole-body vibration (WBV) as add
on to standard pharmacological treatment of osteoporosis (alendronate 70 mg/ week or
raloxifene 60 mg/day) in post-menopausal women.
After informed consent of the patients has been obtained, each patient's potential
eligibility will be assessed during a "Screening Visit". Eligible subjects will be
stratified into two groups: those that are on treatment with alendronate and those that are
on treatment with raloxifene.
Subsequently, at baseline, the patients in each group are randomised to receive either WBV
or no WBV during the first segment of the study. Baseline evaluation of biomarkers of bone
remodelling, fall risk and back pain will be performed before starting the first segment.
Patients will return for efficacy and safety evaluations at week 3 and week 6. At 6 weeks
after baseline the second segment of the study starts: patients that were on WBV during
segment I will be observed for another 6 weeks without WBV, whereas the patients that did
not receive WBV during segment I will now be treated with WBV for 6 weeks in segment II. All
patients will return for additional visits at week 9 and 12 for safety and efficacy
evaluation.
Objectives Primary
1. To establish the effect of whole-body vibration (WBV) on biomarkers of bone remodelling
in postmenopausal women with osteoporosis.
2. To establish the effect of whole-body vibration (WBV) on fall risk and low back pain in
postmenopausal women with osteoporosis.
Secondary
1. To compare the effects of WBV treatment to the effects of treatment without WBV on
biomarkers of bone remodelling, fall risk and low back pain, while keeping standard
pharmacotherapy as a constant parameter
2. To compare the effects of WBV in combination with alendronate to the effects of WBV in
combination with raloxifene on biomarkers of bone remodelling, fall risk and low back
pain
3. To evaluate the long-term effects of WBV on biomarkers of bone remodelling, fall risk
and low back pain
4. Safety of WBV
Study Design Multicentered, randomized study of safety and efficacy of whole-body vibration
(WBV) as add on to standard pharmacological treatment of osteoporosis (alendronate 70 mg/
week or raloxifene 60 mg/day) in post-menopausal women.
After informed consent of the patients has been obtained, each patient's potential
eligibility will be assessed during a "Screening Visit". Eligible subjects will be
stratified into two groups: those that are on treatment with alendronate and those that are
on treatment with raloxifene.
Subsequently, at baseline, the patients in each group are randomised to receive either WBV
or no WBV during the first segment of the study. Baseline evaluation of biomarkers of bone
remodelling, fall risk and back pain will be performed before starting the first segment.
Patients will return for efficacy and safety evaluations at week 3 and week 6. At 6 weeks
after baseline the second segment of the study starts: patients that were on WBV during
segment I will be observed for another 6 weeks without WBV, whereas the patients that did
not receive WBV during segment I will now be treated with WBV for 6 weeks in segment II. All
patients will return for additional visits at week 9 and 12 for safety and efficacy
evaluation.
Number of Subjects Total number: 80 patients Group I: Patients on alendronate, n=40 Group I
a: WBV in segment I, no WBV in segment II, n= 20 Group I b: no WBV in segment I, WBV in
segment II, n=20 Group II: Patients on raloxifene, n=40 Group II a: WBV in segment I, no WBV
in segment II, n= 20 Group II b: no WBV in segment I, WBV in segment II, n=20
Diagnosis / Main Inclusion Criteria Ambulatory postmenopausal women, who had their last
menstrual period at least 2 years before beginning the study Free of severe acute or
chronically disabling conditions with a life expectancy of at least 5 years Expected to
remain ambulatory throughout the entire study and expected to return for all study visits
Expected to be compliant with study procedures, including procedures for WBV usage Women who
have no language barrier, are cooperative, and who give informed consent before entering the
study Women must be on standard therapy with alendronate or raloxifene for at least 3 months
before the commencement of WBV, and their treatment must be expected to remain stable
throughout the study
Main Exclusion Criteria Participation in another clinical study within the last 30 days
and/or during the study Subjects who are inmates of psychiatric wards, prisons, or any other
state institutions Investigators or any other team member involved directly or indirectly in
the conduct of the clinical study Thrombophlebitis, deep venous thrombosis, any
thromboembolic disorders (including pulmonary or retinal embolism) within the last year Any
vascular disorders of the lower extremities with the exception of asymptomatic varicosis
Current bone disorders other than primary osteoporosis, such as hyperparathyroidism, Paget's
disease, renal osteodystrophy, osteomalacia, osteonecrosis, spondylolisthesis Vertebral
fracture or fractures of the lower extremities within the last 6 months before start of WBV
Frequent occurrence of muscle spasms limiting the use of WBV Spastic disorders Morbus Sudeck
(CRPS I) Malignancy within the past 2 years with the exception of in situ removal of basal
cell carcinoma Severe cardiovascular disorder, such as but not limited to: not controllable
hypertension, clinically relevant cardiac arrhythmia and cardiac valve disorder, heart
failure (NYHA III-IV) Cerebral vascular accident within the past 1 year Any
neurologic/psychiatric disorder which might interfere with the conduct of the trial or the
study results such as, but not limited to, the following: Depression, schizophrenia,
dementia, Parkinson's disease, epilepsy Benign Paroxysmal Positional Vertigo Frequent
occurrence of migraine attacks (more than once per month), limiting the use of WBV Active
renal lithiasis or gall stones as defined by any colic within 6 months prior to start of WBV
Acute inflammation, infection and/or fever Immune compromised conditions such as, but not
limited to, rheumatoid arthritis, HIV severe diabetes, e.g. defined by the coexistence of an
arterial occlusive disease Major surgical interventions within 3 months prior to WBV
Metallic or plastic implants like joint implants, pace makers, cardiac valves, stents, eye
lenses that limit the use of WBV Any acute joint inflammation of the lower extremities or
other parts of the body which might interfere with the use of WBV within the last 6 months
before start of WBV Start or change in regimen of physical therapy, or extreme sportive
activity within 1 month prior to study and during the study Treatment with doses of any of
the following medications more recently than 6 months before beginning the study: Androgen,
Calcitonin, Estrogen, Progestin, strontium ranelate, parathormone, proton pump inhibitors
Long term treatment (more than 6 months) with Heparin within the last 2 years Patients in
the alendronate group must be naïve to other bisphosphonates and raloxifen Patients in the
raloxifen group must be naïve to all bisphosphonates Treatment with WBV within the last 6
months Treatment with therapeutic doses of systemic corticosteroids for more than 1 month
during the 12 months before beginning the study Treatment with 50,000 IU or more of vitamin
D once weekly more recently than 3 months before beginning the study
Investigational Medical Device (IMD)
Whole Body Vibration procedure (WBV) will be performed using Fitvibe® medical (Manufacturer:
Uniphy Elektromedizin GmbH & Co. KG, Germany), a certified medical device, in the following
way:
Three Sessions per week of treatment, with a minimum of 15 sessions within a period of 6
weeks One session consists of 10 runs each containing 30 sec vibration intervals with a 15
sec plateau, interrupted by 30 sec pauses Frequency of 30 Hz Amplitude of 2 mm
Efficacy Endpoints Primary
1. Changes in biomarkers of bone formation (Bone specific alcalic phosphatase - Ostase)
and bone resorption (cross links of N-terminal telopeptide of type 1 collagen - N-Tx)
during treatment with WBV
2. Changes in fall risk (Tinetti Mobility test) and low back pain (11 point NAS) during
treatment with WBV
Secondary
1. Changes in Ostase and N-Tx biomarkers during the first 3 weeks of treatment with WBV
2. Changes in Ostase and N-Tx biomarkers during Segment II in Group I a and II a
3. Changes in fall risk (Tinetti Mobility test) and low back pain (11 point NAS) during
the first 3 weeks of treatment with WBV
4. Changes in fall risk (Tinetti Mobility test) and low back pain (11 point NAS) during
Segment II in Group I a and II a
Safety Variables Routine physical examinations, monitoring of vital signs, body height and
adverse events
Statistical Methods The confirmatory analysis is based on the primary criterion "Effect of
WBV", measured with the changes in markers of bone formation Ostase and N-Tx as well as fall
risk and low back pain from start to end of WBV segment of the study (within group
comparison). Since normal distribution cannot be assumed for the test variables, the
Wilcoxon-rank-test will be used as two-sided test on difference.
The final evaluation of the primary criteria will be performed hierarchically in the
following order:
1. "changes in marker Ostase during treatment with WBV"
2. "changes in marker N-Tx during treatment with WBV"
3. "changes in fall risk during treatment with WBV"
4. "changes in low back pain during treatment with WBV"
The hypothesis for the four tests on difference are:
H0: µ1-µ2 = 0 H1: µ1-µ2 = 0 The experiment wise multiple level alpha is defined as alpha =
0.05 two-sided respectively as required for confirmatory studies. If the primary hypothesis
tests are performed in the given order (1. to 4.) the test can be performed with full alpha
as long as the result for the previous test turns to be significant (Principle of a priori
ordered hypotheses).
The confirmatory analysis is performed using the ITT population (intention-to-treat).
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT03162068 -
Cushing's Osteoporosis Specificities
|
N/A |