PTH and Vibration in OSteoporosis Study

Study Overview
=================
Brief Summary
-----------------
Objective: This is a randomized controlled trial (RCT) in osteoporosis patients randomized to standard parathyroid hormone (PTH) treatment alone or to standard PTH treatment and Whole-body vibration (WBV). PTH is an effective but expensive anabolic treatment for osteoporosis. WBV stimulates muscles and bones. A combined treatment might have synergistic or additive beneficial effects on bone, reducing fracture risk making treatment more effective and cost-effective. A beneficial effect on muscles and thereby falls risk of WBV may improve fracture risk even further. If the results of this pilot study are promising then a strong case can be made for a large multi-centre RCT using strong endpoints including fractures and falls.

Detailed Description
-----------------
Study Objectives To determine if WBV in addition to standard PTH treatment has a greater effect on bone mass in osteoporosis patients compared to standard PTH treatment alone. To determine if WBV in addition to standard PTH treatment has a greater effect on bone microarchitecture in osteoporosis patients compared to standard PTH treatment alone, as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). To determine if WBV in addition to standard PTH treatment has a greater effect on markers of bone formation and resorption in osteoporosis patients compared to standard PTH treatment alone. To study the effects of WBV on muscle function and balance in osteoporosis To assess the safety and adherence to WBV in osteoporotic patients Study Design: General Design This will be a multi-center randomized controlled trial (RCT) in osteoporosis patients being started on standard PTH treatment according to Danish Osteoporosis guidelines. Participants will be randomized to standard PTH treatment alone or to standard PTH treatment and WBV. Statistical Plan: Sample Size Determination The inclusion of 32 participants (16 in both groups) would give the study 80% power to detect a clinically significant additional increase of 22% with WBV (assuming a 9% increase of BMD in the PTH alone group and 11% increase in the combined PTH+WBV group, and assuming a SD of the BMD increase of 2%. Allowing for a 20% dropout rate, the plan is to include 40 participants (20 in each group). From previous research on WBV by one of the investigators (TM), statistically significant differences were found in bone formation markers and in muscle strength at 3 months between the WBV and control groups with a sample size of 35. The number of participants in the latter pilot work is reassuringly consistent with the sample size calculations. The number needed to be included is far less (34%) than the actual number of patients treated with PTH in the recruiting departments in a similar time period last year. Statistical Methods: STATA/SPSS will be used for data analysis. For the primary endpoint (BMD at 12 months) the mean percentage changes in BMD between the two groups will be compared using Analysis of Variance (ANOVA) provided the distribution is normal. For the other endpoints parametric tests will be used to assess differences in the two groups for normally distributed data and non-parametric tests for data not normally distributed. The randomization will be done online in the data capture program Red Cap. There will be created a Data dictionary that contains detailed descriptions of each variable used by the registry, including the source of the variable, and normal ranges if relevant. Information: Participants will be recruited during their attendance at the outpatient clinics. At that time the subjects will be given a full explanation of the study as well as the patient information sheet and invited to participate in the study. At an interval of not less than 24 hours, patients will be invited to consent prior to starting their PTH treatment. The information will be sufficient for subjects to make an informed decision about their participation in this study. The subject will complete and sign a consent form to indicate they are giving valid consent to participate in the trial. Withdrawal of Subjects: Patients who withdraw consent from participation in the trial will be withdrawn from the trial. This will not affect their standard medical management and not cause any adverse effect on the subject.

Official Title
-----------------
PTH and Vibration in OSteoporosis (PaVOS) Study

Conditions
-----------------
Osteoporosis

Intervention / Treatment
-----------------
* Other: whole-body vibration
* Drug: teriparatide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women starting PTH treatment for osteoporosis according to Danish Osteoporosis guidelines Exclusion Criteria: Women currently taking oral glucocorticoids Women unable to give informed consent Women unable to stand for 2 minutes at a time on the vibration platform Women who have contraindications to WBV (e.g. joint prosthesis, pacemakers)

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: controlgroup<br>Teriparatide, 20 microgram/day. 24 months of treatment | Drug: teriparatide<br>* Teriparatide, 20 microgram/day. 24 months of treatment.<br>* Other names: PTH;|
| Experimental: studygroup 1<br>Teriparatide, 20 microgram/day. 24 months of treatment. 12 months of Whole-body vibration on vibration platforms. | Other: whole-body vibration<br>* Whole-body vibration on vibration platforms. 30-40 Hertz, from 2 mm (low) to 4 mm (high) amplitude, 1 minutes x 6 with 1 minute break between. 3 times a week.<br>* Other names: vibration therapy;Drug: teriparatide<br>* Teriparatide, 20 microgram/day. 24 months of treatment.<br>* Other names: PTH;|
| Experimental: studygroup 2<br>Teriparatide, 20 microgram/day. 24 months of treatment. 24 months of Whole-body vibration on vibration platforms | Other: whole-body vibration<br>* Whole-body vibration on vibration platforms. 30-40 Hertz, from 2 mm (low) to 4 mm (high) amplitude, 1 minutes x 6 with 1 minute break between. 3 times a week.<br>* Other names: vibration therapy;Drug: teriparatide<br>* Teriparatide, 20 microgram/day. 24 months of treatment.<br>* Other names: PTH;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the BMD, Bone Mineral Density of hip and spine region (Hologic DXA machine) | DXA scan of hip and spine regions, BMD (g/cm^2) | at the time the participants start treatment and in an interval as close as possible to after 6, 12, 18, 24 months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Bone microarchitecture at the tibia | HRpQCT assesses parameters of bone microarchitecture at the tibia. | at the time the participants start treatment and in an interval as close as possible to after 6, 12, 18 and 24 months from baseline | 
| Changes in the Bone microarchitecture at the radius | HRpQCT assesses parameters of bone microarchitecture at the radius. | at the time the participants start treatment and in an interval as close as possible to after 6, 12, 18 and 24 months from baseline | 
| changes in muscle mass | Full body DXA | at the time the participants start treatment and in an interval as close as possible to after 12 and 24 months from baseline | 
| Changes from baseline in the markers of bone resorption | CTX, sclerostin | at the time the participants start treatment and in an interval as close as possible to after 3, 6, 12, 18, 24 months from baseline | 
| Changes from baseline in the markers of bone formation | P1NP | at the time the participants start treatment and in an interval as close as possible to after 3, 6, 12, 18, 24 months from baseline | 
| Changes in Muscle strength | Measurements of muscle strength (leg extensor power) | at the time the participants start treatment and in an interval as close as possible to after 3,6,12,18 and 24 months from baseline | 
| Changes in handgrip strength | Measurements of muscle strength (handgrip strength) | at the time the participants start treatment and in an interval as close as possible to after 3,6,12,18 and 24 months from baseline | 
| Changes in Balance | Short Physical Performance Battery (SPPB) | at the time the participants start treatment and in an interval as close as possible to after 3, 6 ,12, 18 and 24 months from baseline | 
| Adherence to WBV | Self Reporting training log | During 2 years from the start of the treatment | 
| Changes in physical activity | IPAQ short version | at the time the participants start treatment and in an interval as close as possible to after 12, and 24 months from baseline | 
| Changes in quality of life | EQ5D questionaire. | at the time the participants start treatment and in an interval as close as possible to after 12, and 24 months from baseline | 
| Changes in basic mobility | Time up and go test | at the time the participants start treatment and in an interval as close as possible to after 3,6,12,18 and 24 months from baseline | 
| Changes in The Falls Efficacy Scale International | FES-I | at the time the participants start treatment and in an interval as close as possible to after 12, and 24 months from baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
whole body vibration, PTH