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

NCT ID: NCT03208582

Last Updated: 2018-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-01
• Study Completion Date: 2017-11-02

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.

Conditions

Osteogenesis Imperfecta

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Single arm trial

Intervention : Risedronate Sodium (oral) Dosage: 1mg/kg/week Frequency: once/week Duration: 6 weeks

Group Type: OTHER

Risedronate Sodium

Intervention Type: DRUG

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 tablets

Intervention Type: DIETARY_SUPPLEMENT

Participants will take calcichew tablets during the 6 week period of risedronate treatment

Interventions

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

Intervention Type: DRUG

Calcichew tablets

Participants will take calcichew tablets during the 6 week period of risedronate treatment

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Bisphosphonate

Eligibility Criteria

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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheffield Children's NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nick Bishop, MD, FRCPCH

Role: STUDY_CHAIR

Sheffield Children's Hospital and University of Sheffield

Locations

Clinical Research Facility

Sheffield, South Yorkshire, United Kingdom

Countries

United Kingdom

Other Identifiers

SCH-2013

Identifier Type: -

Identifier Source: org_study_id