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

This study has been completed.
Sponsor:
Collaborators:
Research Center for Ageing and Osteoporosis, Copenhagen University Hospital, Copenhagen, Denmark.
University of Sheffield
Information provided by:
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01130428
First received: May 25, 2010
Last updated: April 19, 2011
Last verified: April 2011
  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

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • 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
Criteria

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01130428

Locations
Netherlands
Maastricht University Medical Center
Maastricht, Netherlands, 6200 MD
Sponsors and Collaborators
Maastricht University Medical Center
Research Center for Ageing and Osteoporosis, Copenhagen University Hospital, Copenhagen, Denmark.
University of Sheffield
Investigators
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 September 16, 2014