Post-menopausal OsteoporosisPhase 2NCT00666627
Bisphosphonate Action on the Appendicular Skeleton: Evidence for Differential Effects
A Phase 2 study testing Ibandronate, Risedronate and Alendronate in people with Post-menopausal Osteoporosis, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
A study to determine if the three licensed bisphosphonates (alendronate, ibandronate and risedronate):a) affect the peripheral skeleton differently, as assessed by quantitative ultrasound of bone (QUS), peripheral quantitative computed tomography (pQCT) and dual-energy x-ray absorptiometry (DXA)? b) have different… Read more about this study
- Who is it for?
- Ages 35 to 85 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Post-menopausal Osteoporosis
- What is being tested?
- Ibandronate, Risedronate and Alendronate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 410 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2007to Dec 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 85 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- be female
- at least 5 years post menopausal but <85 years
- BMD T-score (at the lumbar spine or total hip) of less than or equal to
- 2.5, or T-score less than or equal to -1 with a low trauma fracture.
- be ambulatory
- be able and willing to participate in the study and provide written informed consent
Who cannot join
- have evidence of a clinically significant organic disease which could prevent the patient from completing the study
- have a BMI less than 18 or greater than 35
- abuse alcohol or use illicit drugs or who consumed more than 4 servings of any alcoholic beverage one day prior to the visit (i.e., subjects who might be binge drinkers)
- have any history of cancer within the past 5 years excluding skin cancer non melanomas
- have a history of ongoing conditions or diseases known to cause abnormalities of calcium metabolism or skeletal health (secondary osteoporosis)
- Chronic renal disease (as defined by a creatinine clearance of ≤ 30ml/min)
Show all 27Show fewer
- Acute or chronic hepatic disease
- Malabsorption syndromes
- Hyperthyroidism as manifested by TSH outside the lower limit of the normal range
- Hyperparathyroidism
- Hypocalcemia or hypercalcemia
- Osteomalacia
- Cushing's syndrome
- Patient who are currently on glucocorticoid therapy
- have a serum calcium less than 2.2 mmol/l and a PTH above 75ng/l
- have a history of any known condition that would interfere with the assessment of DXA at either lumbar spine or femoral neck
- have markedly abnormal clinical laboratory parameters that are assessed as clinically significant by the investigator
- use any of the following medications within 12 months of starting study drug
- Bisphosphonates (at any dose)
- Use of any fluoride with the exception use for oral hygiene
- Strontium
- Other bone agents (i.e., SERM, isoflavones, HRT etc)
- have participated in another clinical trial involving active therapy 3 months prior to randomisation
- have a history of allergic reaction to bisphosphonates
- patient taking calcium supplements within the last month prior to randomisation
- We will exclude patients with secondary osteoporosis, those who have been on anti-resorptive treatments in the past year, and women less than 5 years since menopause, and those with bilateral fractures in the measurement regions (heel, hip and forearm).
- Have suffered a recent fracture within the last 12 months
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Academic Unit of Bone Metabolism (Sheffield)
Sheffield, South Yorkshire, S5 7AU
About this study
Official title: A 2-year Randomised Parallel Group Trial of Alendronate, Ibandronate and Risedronate for Postmenopausal Osteoporosis in Secondary Care.
A study to determine if the three licensed bisphosphonates (alendronate, ibandronate and risedronate):a) affect the peripheral skeleton differently, as assessed by quantitative ultrasound of bone (QUS), peripheral quantitative computed tomography (pQCT) and dual-energy x-ray absorptiometry (DXA)? b) have different effects on bone cells and their activity as assessed by flow cytometry and biochemical markers of bone cell activity? The aim of the study is to compare the effects of three licensed bisphosphonates on bone quantity and quality. There has been no such study before. Most of the measures of bone quantity and quality used in this protocol have not been studied with any of these three agents. The novelty of the study necessitates the establishment of reference ranges and this explains the need for the inclusion of a group of young women.
Read the detailed description
There have been a number of randomised controlled trials examining the effect of bisphosphonates on fracture risk. The results of these trials have not been uniform, especially in relation to non-vertebral fractures. We have proposed that much of the fracture risk reduction with risedronate can be explained by the reduction in bone resorption markers (Eastell et al, 2003). Each of these three bisphosphonates reduces bone resorption markers, and alendronate and ibandronate are at least as effective as risedronate in this regard. However, there have been few direct comparisons of the different bisphosphonates on surrogate endpoints such as bone mineral density and bone turnover markers. This raises the question of whether the bisphosphonates might affect some other aspect of bone strength, such as 'bone quality'.
The purpose the study is to determine whether three licensed bisphosphonates affect the skeleton differently using a variety of methods (various bone densitometry devices and ultrasound measurements of the bone) at a variety of bone sites (spine, hip, fingers, heel, forearm and leg). These changes will be compared to changes in other markers of bone health such as biochemical markers of bone turnover to help us determine the possible mechanism of action for the different treatments. The study will last for 48 weeks which should be long enough to detect signfiicant changes on bone strength as measured by DXA at the spine/hip. As we are interested in how these changes occur there are more visits in the first three months of the study than the last 9 months of the study. This is expected to help us detect the difference between the onset of the effects of the three treatments more clearly.
Study vists will be: screening, baseline 1, baseline 2, 1 week, 2 weeks, 4 weeks, 12 weeks, 13 weeks (phone calls to participants at 24 and 36 weeks), 48 weeks and 49 weeks. The two baseline visits will allow duplicate measurements of bone stregth/quality on different occasions at the start of the study to minimise variability. Treatment will begin at baseline 2 (0 days) and last for 48 weeks. The visits at 13 weeks and 49 weeks are to perform bone density/quality tests in duplicate to minimise variability as at baseline visit.
Bone mineral density of various bones (hip/spine/whole body and forearm) will be measured by DXA on various devices, quantitative ultrasound will be performed at the heel and fingers, and bone quality will be measured by pQCT at the forearm and tibia/3D analysis of the hip scans at the baseline visits, at 12 and 13 weeks and at 48 and 49 week visits Surrogate markers of bone health (biochemical markers of bone turnover) will be measured at baseline, 1, 2 4, 12, 13, 48 and 49 weeks. Exploratory methods included in the protocol include: Assessing the number of bone breaking down cell numbers (osteoclasts) at baseline, 1 week and 48 weeks Assessing nail brittleness at baseline 12 and 48 weeks.
Subjects will be randomised using a stratification method to ensure all groups have an equal range of bone strength at study entry. Randomisation will be performed by the hospital pharmacy. The study is not blinded and subjects will know which treatment they are on. Subjects will be asked not to discuss their assigned treatment with staff performing bone measurements. There is no placebo group in this trial as all subjects will taking one of the three treatments. We have chosen the active comparator design as many of the measurements (especially the biochemical and cellular ones) do not change unless treatment is given; also, these treatments are indicated and effective in this patients group.
To generate control data we will recruit a group of 200 healthy young women aged 35-40 years. The control group will undertake all the measurements of bone strength/quality that the treatment group will have as well as the biochemical maerkers of bone turnover. There will be only 2 study visits for the control group,baseline and 48 weeks. This data will serve as internal controls and as reference ranges for each of the devices used in the study. Ethical considerations for this study include the use of ionising radiation, blood sampling at each study visit and the number of study visits. This may be balanced by the close monitoring of the subject whilst on the study and a thorough assessment of bone health for 49 weeks. Research participants, patient groups or communities were not involved in the design of this research study.
The hypothesis of the study is that bisphosphonates have varying magnitude of effect on non-vertebral fractures and this is reflected in different changes in measures of bone quality (QUS), bone density in the appendicular skeleton (DXA and pQCT) and novel biochemical markers of bone resorption and osteoclast precursors.
- Conditions
- Post-menopausal Osteoporosis
- Being tested
- Ibandronate, Risedronate, Alendronate
- Keywords
- Osteoporosis, Post-menopausal osteoporosis, Bisphosphonates, Alendronate, Ibandronate, Risedronate
- Medical subject headings
- Osteoporosis, Postmenopausal, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbandronateDrug
Also called Bonviva
once monthly
RisedronateDrug
Also called Actonel
Risedronate 35mg once weekly
AlendronateDrug
Also called Fosamax
Alendronate 70mg once weekly
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Ibandronate Receives: Drug: Ibandronate |
| 2 | Active comparator | Risedronate Receives: Drug: Risedronate |
| 3 | Active comparator | Alendronate 70mg once weekly Receives: Drug: Alendronate |
| 4 | No intervention | Young women control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heel broadband ultrasound attenuation
Measured: 2 years
Secondary outcomes (9)
Changes in the percentage of MCSFR+ monocytes in the peripheral blood at baseline and after one week and 48 weeks of therapy
Measured: 2 years
Change in SOS at finger and heel at 48 weeks.
Measured: 2 years
Change in lumbar spine and total hip BMD measured by DXA at 48 weeks
Measured: 2 years
Change in finger BMD measured by RA at 48 weeks
Measured: 2 years
Change in heel BMD measured by DXL at 48 weeks
Measured: 2 years
Change in distal tibia and ultradistal forearm cortical and trabecular volumetric BMD by pQCT at 48 weeks
Measured: 2 years
Changes in cathepsin K and MM enzyme and OPG and RANK-L protein at 12 weeks
Measured: 12 weeks
Changes in uNTX and uCTX. At 12 weeks
Measured: 12 weeks
Change in disulfide bond content of nails at 48 weeks
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2008 (estimated)
- Study startApr 2007
- Primary completionSep 2012
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-menopausal OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 410 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Procter and Gamble, University of Sheffield
- Investigators
- Eugene McCloskey, Dr, Study director, University of SheffieldRosemary Hannon, Dr, Study director, University of SheffieldAngela Rogers, Dr, Study director, University of SheffieldMargaret Paggiosi, Dr, Study director, University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00666627
- Sponsor's protocol ID
- STH 14463
- Status last verified
- Mar 2018
- First submitted
- 23 Apr 2008
- Last updated
- 6 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 2-year Randomised Parallel Group Trial of Alendronate, Ibandronate and Risedronate for Postmenopausal Osteoporosis in Secondary Care.
- ClinicalTrials.gov ID
- NCT00666627
- Acronym / sponsor ID
- STH 14463
- Conditions
- Post-menopausal Osteoporosis
- Keywords
- Osteoporosis, Post-menopausal osteoporosis, Bisphosphonates, Alendronate, Ibandronate, Risedronate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 410 participants (estimated)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Procter and Gamble, University of Sheffield
- Study start
- Apr 2007 (actual)
- Primary completion
- Sep 2012 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 25 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to determine if the three licensed bisphosphonates (alendronate, ibandronate and risedronate):a) affect the peripheral skeleton differently, as assessed by quantitative ultrasound of bone (QUS), peripheral quantitative computed tomography (pQCT) and dual-energy x-ray absorptiometry (DXA)? b) have different effects on bone cells and their activity as assessed by flow cytometry and biochemical markers of bone cell activity? The aim of the study is to compare the effects of three licensed bisphosphonates on bone quantity and quality. There has been no such study before. Most of the measures of bone quantity and quality used in this protocol have not been studied with any of these three agents. The novelty of the study necessitates the establishment of reference ranges and this explains the need for the inclusion of a group of young women.
Detailed description
There have been a number of randomised controlled trials examining the effect of bisphosphonates on fracture risk. The results of these trials have not been uniform, especially in relation to non-vertebral fractures. We have proposed that much of the fracture risk reduction with risedronate can be explained by the reduction in bone resorption markers (Eastell et al, 2003). Each of these three bisphosphonates reduces bone resorption markers, and alendronate and ibandronate are at least as effective as risedronate in this regard. However, there have been few direct comparisons of the different bisphosphonates on surrogate endpoints such as bone mineral density and bone turnover markers. This raises the question of whether the bisphosphonates might affect some other aspect of bone strength, such as 'bone quality'.
The purpose the study is to determine whether three licensed bisphosphonates affect the skeleton differently using a variety of methods (various bone densitometry devices and ultrasound measurements of the bone) at a variety of bone sites (spine, hip, fingers, heel, forearm and leg). These changes will be compared to changes in other markers of bone health such as biochemical markers of bone turnover to help us determine the possible mechanism of action for the different treatments. The study will last for 48 weeks which should be long enough to detect signfiicant changes on bone strength as measured by DXA at the spine/hip. As we are interested in how these changes occur there are more visits in the first three months of the study than the last 9 months of the study. This is expected to help us detect the difference between the onset of the effects of the three treatments more clearly.
Study vists will be: screening, baseline 1, baseline 2, 1 week, 2 weeks, 4 weeks, 12 weeks, 13 weeks (phone calls to participants at 24 and 36 weeks), 48 weeks and 49 weeks. The two baseline visits will allow duplicate measurements of bone stregth/quality on different occasions at the start of the study to minimise variability. Treatment will begin at baseline 2 (0 days) and last for 48 weeks. The visits at 13 weeks and 49 weeks are to perform bone density/quality tests in duplicate to minimise variability as at baseline visit.
Bone mineral density of various bones (hip/spine/whole body and forearm) will be measured by DXA on various devices, quantitative ultrasound will be performed at the heel and fingers, and bone quality will be measured by pQCT at the forearm and tibia/3D analysis of the hip scans at the baseline visits, at 12 and 13 weeks and at 48 and 49 week visits Surrogate markers of bone health (biochemical markers of bone turnover) will be measured at baseline, 1, 2 4, 12, 13, 48 and 49 weeks. Exploratory methods included in the protocol include: Assessing the number of bone breaking down cell numbers (osteoclasts) at baseline, 1 week and 48 weeks Assessing nail brittleness at baseline 12 and 48 weeks.
Subjects will be randomised using a stratification method to ensure all groups have an equal range of bone strength at study entry. Randomisation will be performed by the hospital pharmacy. The study is not blinded and subjects will know which treatment they are on. Subjects will be asked not to discuss their assigned treatment with staff performing bone measurements. There is no placebo group in this trial as all subjects will taking one of the three treatments. We have chosen the active comparator design as many of the measurements (especially the biochemical and cellular ones) do not change unless treatment is given; also, these treatments are indicated and effective in this patients group.
To generate control data we will recruit a group of 200 healthy young women aged 35-40 years. The control group will undertake all the measurements of bone strength/quality that the treatment group will have as well as the biochemical maerkers of bone turnover. There will be only 2 study visits for the control group,baseline and 48 weeks. This data will serve as internal controls and as reference ranges for each of the devices used in the study. Ethical considerations for this study include the use of ionising radiation, blood sampling at each study visit and the number of study visits. This may be balanced by the close monitoring of the subject whilst on the study and a thorough assessment of bone health for 49 weeks. Research participants, patient groups or communities were not involved in the design of this research study.
The hypothesis of the study is that bisphosphonates have varying magnitude of effect on non-vertebral fractures and this is reflected in different changes in measures of bone quality (QUS), bone density in the appendicular skeleton (DXA and pQCT) and novel biochemical markers of bone resorption and osteoclast precursors.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: IbandronateIbandronate |
| 2 | Active comparator | Drug: RisedronateRisedronate |
| 3 | Active comparator | Drug: AlendronateAlendronate 70mg once weekly |
| 4 | No intervention | –Young women control group |
Who may qualify
- Ages
- 35 to 85 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- be female
- at least 5 years post menopausal but <85 years
- BMD T-score (at the lumbar spine or total hip) of less than or equal to
- be ambulatory
- be able and willing to participate in the study and provide written informed consent
Key exclusion criteria (27 listed)
- have evidence of a clinically significant organic disease which could prevent the patient from completing the study
- have a BMI less than 18 or greater than 35
- abuse alcohol or use illicit drugs or who consumed more than 4 servings of any alcoholic beverage one day prior to the visit (i.e., subjects who might be binge drinkers)
- have any history of cancer within the past 5 years excluding skin cancer non melanomas
- have a history of ongoing conditions or diseases known to cause abnormalities of calcium metabolism or skeletal health (secondary osteoporosis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbandronateAlso: Bonvivaonce monthly | Drug | 1 |
| RisedronateAlso: ActonelRisedronate 35mg once weekly | Drug | 2 |
| AlendronateAlso: FosamaxAlendronate 70mg once weekly | Drug | 3 |
Primary outcome
Change in heel broadband ultrasound attenuation
Time frame: 2 years
9 secondary outcomes
Changes in the percentage of MCSFR+ monocytes in the peripheral blood at baseline and after one week and 48 weeks of therapy
Time frame: 2 years
Change in SOS at finger and heel at 48 weeks.
Time frame: 2 years
Change in lumbar spine and total hip BMD measured by DXA at 48 weeks
Time frame: 2 years
Change in finger BMD measured by RA at 48 weeks
Time frame: 2 years
Change in heel BMD measured by DXL at 48 weeks
Time frame: 2 years
Change in distal tibia and ultradistal forearm cortical and trabecular volumetric BMD by pQCT at 48 weeks
Time frame: 2 years
Changes in cathepsin K and MM enzyme and OPG and RANK-L protein at 12 weeks
Time frame: 12 weeks
Changes in uNTX and uCTX. At 12 weeks
Time frame: 12 weeks
Change in disulfide bond content of nails at 48 weeks
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eugene McCloskey, Dr study director
University of Sheffield
Rosemary Hannon, Dr study director
University of Sheffield
Angela Rogers, Dr study director
University of Sheffield
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibandronate, Risedronate and Alendronate in people with Post-menopausal Osteoporosis, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in heel broadband ultrasound attenuation (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2018.