Osteogenesis ImperfectaPhase 2BAMESNCT03208582
Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
A Phase 2 study testing Risedronate Sodium and Calcichew tablets in people with Osteogenesis Imperfecta, run by Sheffield Children's NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Osteogenesis Imperfecta(OI) is an inherited disorder characterised by extreme fragility of the bones. Bones often break from little or no apparent cause. Current available medicine can increase bone strength by making bones wider and "filling in" the holes in the bone walls that weaken it. Read more about this study
- Who is it for?
- Ages 4 to 16 years
- Conditions the study is for
- Osteogenesis Imperfecta
- What is being tested?
- Risedronate Sodium and Calcichew tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2017to 2 Nov 2017
- 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 4 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 4-16 years
- Able to speak fluent English
- Diagnosed with osteogenesis imperfecta
- Able to stand
- Not treated with bisphosphonates
Who cannot join
- Presence of other chronic illnesses
- Balance problems
- Recent fracture (in the last 6 months)
- Recent (last 12 months) or current treatment likely to affect bone - this does not include inhaled or intermittent oral therapy with steroids for asthma
- Involvement in another interventional research project
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Facility
Sheffield, South Yorkshire, S10 2TH
About this study
Osteogenesis Imperfecta(OI) is an inherited disorder characterised by extreme fragility of the bones. Bones often break from little or no apparent cause.
Current available medicine can increase bone strength by making bones wider and "filling in" the holes in the bone walls that weaken it. These medicines are bisphosphonates, given either by a drip intravenously (eg pamidronate), or taken by mouth (eg risedronate). Their major action is to prevent bone breakdown by stopping the normal process of removing and then replacing old bone tissue, so in some parts of the bone, new bone formation is actually reduced. Most studies of bisphosphonates in children with OI have shown increased bone mineral density and improved exercise tolerance that could positively affect new bone formation; some have shown reduced fracture rate. Bone is highly responsive to mechanical stimulation. Whole body vibration (WBV) is a form of mechanical stimulation that has been shown to improve bone mineral density in some individuals with narrow bones.
Read more
Little is known whether bisphosphonates affect the response of the skeleton to mechanical stimulation. We will determine the response to mechanical stimulation in children with OI by looking at bone turnover markers following WBV in those who are and are not treated with bisphosphonates.
The results from this study will help us to understand whether skeleton in children with OI is normally responsive to mechanical stimulation, and whether bisphosphonates alter that responsiveness in a way that is either beneficial or not for increasing bone strength.
Read the detailed description
Essentially, subjects will have a baseline assessment (WBV1) of their bone turnover marker response to a week-long period of whole body vibration (10 minutes/day), followed by a "washout period" of 5 weeks during which bone turnover is expected to return to normal. Following this, there will be a period of 6 weeks of treatment with risedronate (1 mg/kg/week). Immediately following this will come a second assessment (WBV2) of the bone turnover marker response to a week-long period of whole body vibration (10 minutes/day) as previously.
The subjects stand on the vibration platform for 10 minutes for 7 days on 2 occasions. The vibration is delivered as 4 "blocks" of 2.5 minutes each, with 30 seconds rest in between each block. The initial Whole Body Vibration (WBV) on day 1 will be undertaken in the Sheffield Children's Hospital Clinical Research Facility (SCHCRF) under supervision. Subsequent WBVs D2-D7 and D85-91 will be done in the participants' homes. Participants will be asked to record the administration and timing of WBV in a diary.
Blood samples will be taken after an overnight fast according to the following schedule:
Pre-WBV1 D1; D8 (postWBV); D15; D43 (immediate pre-risedronate); D85 (post-risedronate and pre-WBV2); D92 (post-WBV2) and D99 (final). 7 samples are taken altogether.
The blood tests are bone turnover markers (Alkaline phosphatase[ALP], Procollagen Type 1 N-Terminal Propeptide[P1NP] and C-Terminal Telopeptide of Type 1 Collagen[CTX]). The first blood test will be done by the researcher (Dr Sithambaram) in the SCHCRF and the subsequent 6 blood tests can be done by the research nurse/researcher at the participant's home. Blood samples taken will be allowed to clot for ½ an hour. Samples will be spun at 2500 rpm for 10 minutes at 4°C. The centrifuged sample will be stored in SCHCRF at -80°C. Blood tests will be analysed in the Mellanby Centre for Bone Research, University of Sheffield.
Participants will be taking risedronate (oral bisphosphonate, once weekly), rounded to the nearest 5 mg) together with Vitamin D and calcium for 6 weeks. Vitamin D and Calcium will be given as Calcichew 500mg/200 IU tablets, 1 tablet for participants weighing less than 30 kg and 2 tablets for participants weighing 30 kg or more. Risedronate Sodium belongs to Bisphosphonates group of medicine. As per BNF, it is not licensed for use in children. The trade name is Actonel® Warner Chilcott). This study will use 5mg and 35mg film-coated tablets.
- Conditions
- Osteogenesis Imperfecta
- Being tested
- Risedronate Sodium, Calcichew tablets
- Medical subject headings
- Osteogenesis Imperfecta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Risedronate SodiumDrug
Also called Bisphosphonate
Participants will be initially tested on the response to mechanical stimulation as a baseline and then tested again after 6 weeks treatment with Risedronate
Calcichew tabletsDietary supplement
Participants will take calcichew tablets during the 6 week period of risedronate treatment
| Study group | Role | What they receive |
|---|---|---|
| Single arm trial | Other | Intervention : Risedronate Sodium (oral) Dosage: 1mg/kg/week Frequency: once/week Duration: 6 weeks Receives: Drug: Risedronate Sodium; Dietary Supplement: Calcichew tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in P1NP response to 1 week of vibration without risedronate treatment, followed by a washout period. Change in P1NP response to vibration will be reassessed following Risedonate treatment. Serial bone markers will be done over a 99 day period.
To assess if risedronate alters the response to mechanical stimulation
Measured: 99 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2017
- Study start1 Apr 2017
- Primary completion2 Nov 2017
- Study completion2 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteogenesis ImperfectaStudies 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Children's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nick Bishop, MD, FRCPCH, Study chair, Sheffield Children's Hospital and University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03208582
- Sponsor's protocol ID
- SCH-2013
- Acronym
- BAMES
- Status last verified
- May 2017
- First submitted
- 23 May 2017
- Last updated
- 7 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
- ClinicalTrials.gov ID
- NCT03208582
- Acronym / sponsor ID
- BAMES / SCH-2013
- Conditions
- Osteogenesis Imperfecta
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Sheffield Children's NHS Foundation TrustUniversity, hospital or other
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 2 Nov 2017 (actual)
- Study completion
- 2 Nov 2017 (actual)
- First posted
- 5 Jul 2017 (actual)
- 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.
Osteogenesis Imperfecta(OI) is an inherited disorder characterised by extreme fragility of the bones. Bones often break from little or no apparent cause.
Current available medicine can increase bone strength by making bones wider and "filling in" the holes in the bone walls that weaken it. These medicines are bisphosphonates, given either by a drip intravenously (eg pamidronate), or taken by mouth (eg risedronate). Their major action is to prevent bone breakdown by stopping the normal process of removing and then replacing old bone tissue, so in some parts of the bone, new bone formation is actually reduced. Most studies of bisphosphonates in children with OI have shown increased bone mineral density and improved exercise tolerance that could positively affect new bone formation; some have shown reduced fracture rate. Bone is highly responsive to mechanical stimulation. Whole body vibration (WBV) is a form of mechanical stimulation that has been shown to improve bone mineral density in some individuals with narrow bones.
Little is known whether bisphosphonates affect the response of the skeleton to mechanical stimulation. We will determine the response to mechanical stimulation in children with OI by looking at bone turnover markers following WBV in those who are and are not treated with bisphosphonates.
The results from this study will help us to understand whether skeleton in children with OI is normally responsive to mechanical stimulation, and whether bisphosphonates alter that responsiveness in a way that is either beneficial or not for increasing bone strength.
Detailed description
Essentially, subjects will have a baseline assessment (WBV1) of their bone turnover marker response to a week-long period of whole body vibration (10 minutes/day), followed by a "washout period" of 5 weeks during which bone turnover is expected to return to normal. Following this, there will be a period of 6 weeks of treatment with risedronate (1 mg/kg/week). Immediately following this will come a second assessment (WBV2) of the bone turnover marker response to a week-long period of whole body vibration (10 minutes/day) as previously.
The subjects stand on the vibration platform for 10 minutes for 7 days on 2 occasions. The vibration is delivered as 4 "blocks" of 2.5 minutes each, with 30 seconds rest in between each block. The initial Whole Body Vibration (WBV) on day 1 will be undertaken in the Sheffield Children's Hospital Clinical Research Facility (SCHCRF) under supervision. Subsequent WBVs D2-D7 and D85-91 will be done in the participants' homes. Participants will be asked to record the administration and timing of WBV in a diary.
Blood samples will be taken after an overnight fast according to the following schedule:
Pre-WBV1 D1; D8 (postWBV); D15; D43 (immediate pre-risedronate); D85 (post-risedronate and pre-WBV2); D92 (post-WBV2) and D99 (final). 7 samples are taken altogether.
The blood tests are bone turnover markers (Alkaline phosphatase[ALP], Procollagen Type 1 N-Terminal Propeptide[P1NP] and C-Terminal Telopeptide of Type 1 Collagen[CTX]). The first blood test will be done by the researcher (Dr Sithambaram) in the SCHCRF and the subsequent 6 blood tests can be done by the research nurse/researcher at the participant's home. Blood samples taken will be allowed to clot for ½ an hour. Samples will be spun at 2500 rpm for 10 minutes at 4°C. The centrifuged sample will be stored in SCHCRF at -80°C. Blood tests will be analysed in the Mellanby Centre for Bone Research, University of Sheffield.
Participants will be taking risedronate (oral bisphosphonate, once weekly), rounded to the nearest 5 mg) together with Vitamin D and calcium for 6 weeks. Vitamin D and Calcium will be given as Calcichew 500mg/200 IU tablets, 1 tablet for participants weighing less than 30 kg and 2 tablets for participants weighing 30 kg or more. Risedronate Sodium belongs to Bisphosphonates group of medicine. As per BNF, it is not licensed for use in children. The trade name is Actonel® Warner Chilcott). This study will use 5mg and 35mg film-coated tablets.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm trial | Other | Drug: Risedronate Sodium, Dietary Supplement: Calcichew tabletsIntervention : Risedronate Sodium (oral) Dosage: 1mg/kg/week Frequency: once/week Duration: 6 weeks |
Who may qualify
- Ages
- 4 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Age 4-16 years
- Able to speak fluent English
- Diagnosed with osteogenesis imperfecta
- Able to stand
- Not treated with bisphosphonates
Key exclusion criteria (5 listed)
- Presence of other chronic illnesses
- Balance problems
- Recent fracture (in the last 6 months)
- Recent (last 12 months) or current treatment likely to affect bone - this does not include inhaled or intermittent oral therapy with steroids for asthma
- Involvement in another interventional research project
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 |
|---|---|---|
| Risedronate SodiumAlso: BisphosphonateParticipants will be initially tested on the response to mechanical stimulation as a baseline and then tested again after 6 weeks treatment with Risedronate | Drug | Single arm trial |
| Calcichew tabletsParticipants will take calcichew tablets during the 6 week period of risedronate treatment | Dietary supplement | Single arm trial |
Primary outcome
Change in P1NP response to 1 week of vibration without risedronate treatment, followed by a washout period. Change in P1NP response to vibration will be reassessed following Risedonate treatment. Serial bone markers will be done over a 99 day period.
Time frame: 99 days
To assess if risedronate alters the response to mechanical stimulation
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 7 Sep 2018.
- Individual participant dataSharing planned: Undecided
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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.
Nick Bishop, MD, FRCPCH study chair
Sheffield Children's Hospital and 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 Risedronate Sodium and Calcichew tablets in people with Osteogenesis Imperfecta, run by Sheffield Children's 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 5 inclusion and 5 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 7 Sep 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 P1NP response to 1 week of vibration without risedronate treatment, followed by a washout period. Change in P1NP response to vibration will be reassessed following Risedonate treatment. Serial bone markers will be done over a 99 day period. (time frame: 99 days). 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 7 Sep 2018.