Mechanical Bone Stimulation and Adenosine 5'-Triphosphate (ATP) Release in Humans

Osteoporosis Clinical Trial

Official title:

Pilot Study on the Effect of Mechanical Stimulation of Bone on ATP Release in Humans in Vivo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01130428
• Other study ID #: MEC 10-3-026
• Secondary ID: ATPBone-WP7.2
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 25, 2010
• Last updated: April 19, 2011
• Start date: October 2010
• Est. completion date: December 2010

Study information

• Verified date: April 2011
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Rationale: Mechanical loading is well-known to have a strong anabolic effect on bone. It has therefore been proposed that a mechanical intervention could be an effective non-pharmacological approach to treat bone loss associated with conditions such as osteopenia and osteoporosis. Data from in vitro experiments indicate that the purine nucleotide adenosine 5'-triphosphate (ATP) is released by bone cells and mediates cellular crosstalk via P2 purinergic receptors in response to mechanical stimulation. ATP release by bone cells may thus be part of a general mechanism by which mechanical loading ultimately results in increased bone formation, but this remains to be investigated in humans in vivo. The investigators hypothesize that a mechanical intervention in humans leads to a rise in systemic ATP concentrations due to ATP release from bone.

Objective: To investigate in vivo whether a measurable increase in systemic ATP levels occurs in response to mechanical stimulation of bone in humans.

Study design: Intervention study with a non-randomized, non-blinded design. All subjects will participate in a single experiment, lasting approximately 3 hours, during which the subjects will receive a mechanical intervention at a fixed dose.

Study population: Maximally 10 healthy human volunteers (18-35 y). Intervention: Subjects will receive a gentle and safe mechanical intervention, which will be administered by means of a Juvent 1000 Vibration Platform delivering low-magnitude mechanical stimuli (i.e. vibrations) to the forearm. The mechanical stimulation will be administered at a frequency of 90 Hz and amplitude of 10 µm in an intermittent fashion, i.e. three 10-minute periods of stimulation with 10-minute rest periods in between.

Main outcome parameters: As the primary outcome parameter, a change in extracellular ATP concentrations as a result of the mechanical intervention will be assessed systemically.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Healthy human volunteers;

• Age 18-35 years;

• Cannulation of veins in forearm possible;

• Written informed consent.

Exclusion Criteria:

• Metabolic bone disease (osteoporosis, Paget's Disease, hyperparathyroidism, osteomalacia) or any other condition affecting bone metabolism (e.g. corticoid-treated rheumatoid arthritis);

• Recent bone fracture of any kind = 12 months preceding the study;

• Blood donors.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Device:
• Juvent 1000 Vibration Platform
As a mechanical intervention, mechanical stimulation in the form of vibration will be administered to the forearm using a Juvent 1000 Vibration Platform (Juvent Medical, Inc., Lakeland, FL, USA), which is a non-medicinal product. The device produces gentle, low-magnitude mechanical signals in the form of low-amplitude vertical displacements at a high frequency. The intervention in the present study will be given at a fixed dosage that is defined by the intensity of vibration: frequency: 90 Hz, amplitude: 10 µm (~3.0 g). The mechanical stimulation will be administered in an intermittent fashion, as it has been shown that inserting short rest periods between loading cycles enhances the efficacy of mechanical loading [38]. Thus, the mechanical stimulation will be administered for three times 10 minutes (i.e. the vibration platform turned on), with 10-minute rest periods in between (i.e. the vibration platform turned off); the intervention will have a total duration of 50 minutes.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht

Sponsors (3)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Research Center for Ageing and Osteoporosis, Copenhagen University Hospital, Copenhagen, Denmark., University of Sheffield

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in systemic ATP levels in response to mechanical stimulation	As the primary outcome parameter, ATP release from bone after a mechanical intervention will be investigated in humans in vivo by assessing a change in systemic concentrations of ATP and its metabolites in response to mechanical stimulation as an objective outcome measure. A change in levels of ATP (or its metabolites) is defined as the average of three concentrations after the intervention minus the average of three concentrations before the intervention (i.e. baseline).	Pre-post treatment comparison	No

External Links

•   website ATP research at Maastricht University Medical Center
•   website EU project on the role of purinergic P2 receptor signalling in bone metabolism and osteoporosis