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Trial record 10 of 41 for:    Interventional Studies | Osteogenesis Imperfecta

Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta? (BAMES)

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ClinicalTrials.gov Identifier: NCT03208582
Recruitment Status : Completed
First Posted : July 5, 2017
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
Sheffield Children's NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE May 23, 2017
First Posted Date  ICMJE July 5, 2017
Last Update Posted Date September 7, 2018
Actual Study Start Date  ICMJE April 1, 2017
Actual Primary Completion Date November 2, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
Official Title  ICMJE Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Osteogenesis Imperfecta
Intervention  ICMJE
  • Drug: Risedronate Sodium
    Participants will be initially tested on the response to mechanical stimulation as a baseline and then tested again after 6 weeks treatment with Risedronate
    Other Name: Bisphosphonate
  • Dietary Supplement: Calcichew tablets
    Participants will take calcichew tablets during the 6 week period of risedronate treatment
Study Arms  ICMJE Single arm trial
Intervention : Risedronate Sodium (oral) Dosage: 1mg/kg/week Frequency: once/week Duration: 6 weeks
Interventions:
  • Drug: Risedronate Sodium
  • Dietary Supplement: Calcichew tablets
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 6, 2018)
13
Original Estimated Enrollment  ICMJE
 (submitted: July 3, 2017)
15
Actual Study Completion Date  ICMJE November 2, 2017
Actual Primary Completion Date November 2, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 4-16 years
  • Able to speak fluent English
  • Diagnosed with osteogenesis imperfecta
  • Able to stand
  • Not treated with bisphosphonates

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03208582
Other Study ID Numbers  ICMJE SCH-2013
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Sheffield Children's NHS Foundation Trust
Study Sponsor  ICMJE Sheffield Children's NHS Foundation Trust
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Nick Bishop, MD, FRCPCH Sheffield Children's Hospital and University of Sheffield
PRS Account Sheffield Children's NHS Foundation Trust
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP