Mechanical Bone Stimulation and Adenosine 5'-Triphosphate (ATP) Release in Humans
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Osteoporosis |
Device: Juvent 1000 Vibration Platform |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science |
| Official Title: | Pilot Study on the Effect of Mechanical Stimulation of Bone on ATP Release in Humans in Vivo |
- Change in systemic ATP levels in response to mechanical stimulation [ Time Frame: Pre-post treatment comparison ] [ Designated as safety issue: No ]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).
| Estimated Enrollment: | 10 |
| Study Start Date: | October 2010 |
| Study Completion Date: | December 2010 |
| Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Intervention group
As a mechanical intervention, we will use a vibration platform to administer mechanical stimulation to the forearm of subjects (see Figure 1). All subjects will participate in a single experiment during which they will receive the mechanical intervention a fixed dose of; the duration of an experiment is approximately three hours.
|
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. |
Eligibility| Ages Eligible for Study: | 18 Years to 35 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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.
Contacts and Locations| Netherlands | |
| Maastricht University Medical Center | |
| Maastricht, Netherlands, 6200 MD | |
| Study Chair: | PC Dagnelie, PhD | Maastricht University Medical Center, Department of Epidemiology |
| Principal Investigator: | MJL Bours, PhD | Maastricht University Medical Center, Department of Epidemiology |
More Information
Additional Information:
No publications provided
| Responsible Party: | PC Dagnelie PhD, Maastricht University Medical Center |
| ClinicalTrials.gov Identifier: | NCT01130428 History of Changes |
| Other Study ID Numbers: | MEC 10-3-026, ATPBone-WP7.2 |
| Study First Received: | May 25, 2010 |
| Last Updated: | April 19, 2011 |
| Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Keywords provided by Maastricht University Medical Center:
|
Mechanical stimulation Vibration platform Bone metabolism ATP release |
Additional relevant MeSH terms:
|
Osteoporosis Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases |
ClinicalTrials.gov processed this record on May 21, 2013