Micromechanical Modeling Using Low Magnitude Mechanical Stimulation

NCT ID: NCT01921517

Last Updated: 2019-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2019-06-20

Brief Summary

The response to a daily 10 minute session of low-magnitude mechanical stimulation (LMMS) on bone in 100 postmenopausal women ages 45-65 years will be evaluated at baseline and 12 months using high-resolution magnetic resonance (MR) imaging. Subjects will be assigned to an active platform that produces vibrations or to a placebo platform that produces no vibrations.

The investigators propose to evaluate the hypothesis that LMMS applied to postmenopausal women ages 45-65 improves the mechanical integrity of bone while lowering marrow adiposity.

1. The investigators will optimize an integrated imaging protocol for high-resolution structural MR imaging of the distal tibia and spectroscopic imaging-based quantification of bone marrow composition in the lumbar vertebrae.

2. The investigators will further develop and validate micro-finite-element (FE) analysis for quantitative assessment of trabecular and cortical bone stiffness and failure load from high-resolution MR images of the distal tibia.

3. The investigators will apply the methodology of Aims 1 and 2 (above) in a double-blinded, randomized, placebo-controlled study to a cohort of 100 healthy postmenopausal women in the age range of 45-65 years, studied at baseline and 12 months after having been subjected to 10 minutes daily of either 30 Hz/0.3g stimulation or placebo treatment, monitored rigorously via electronic feedback.

Detailed Description

Weightbearing exercise has an osteogenic effect by reducing bone resorption and enhancing bone formation. During the past several years a number of articles have appeared demonstrating that low-magnitude mechanical stimulation (LMMS) is osteogenic in animals and also in humans. Preclinical studies have also demonstrated an effect of decrease in adiposity. The mechanobiology underlying these phenomena is beginning to emerge in terms of expression of genes stimulated by the action of the vibrations to which osteocytes and adipocytes are subjected.

If successful, LMMS treatment, a non-pharmacologic intervention, could prevent bone loss and potentially stimulate bone formation and decreased adipocyte production resulting in increased bone strength and reduced fracture susceptibility in subjects at risk of developing osteoporosis. The proposed project focuses directly on measures of strength by evaluating the therapeutic response in terms of magnetic resonance (MR) image-based micro finite-element (FE) assessment of bone stiffness and failure strength, along with quantifying treatment-induced changes in marrow adiposity, as part of a single, integrated examination, conducted at baseline and 12 months of treatment in a double-blinded, randomized, placebo-controlled study of early postmenopausal women.

Conditions

Bone Alteration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Low Magnitude Mechanical Stimulation

10 minutes daily of 30 Hz/0.3g stimulation using a vibrating platform.

Group Type: EXPERIMENTAL

Low Magnitude Mechanical Stimulation

Intervention Type: DEVICE

Mechanical stimulation for 10 minutes daily for 12 months at a frequency of 30 Hz and acceleration of 0.3 g.

Sham Low Magnitude Mechanical Stimulation

10 minutes daily of placebo treatment using a sham vibrating platform.

Group Type: PLACEBO_COMPARATOR

Sham Low Magnitude Mechanical Stimulation

Intervention Type: DEVICE

Mechanical stimulation for 10 minutes daily for 12 months using a sham device.

Interventions

Low Magnitude Mechanical Stimulation

Mechanical stimulation for 10 minutes daily for 12 months at a frequency of 30 Hz and acceleration of 0.3 g.

Intervention Type: DEVICE

Sham Low Magnitude Mechanical Stimulation

Mechanical stimulation for 10 minutes daily for 12 months using a sham device.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Females, ages 45-65 years and post menopausal, as defined by a history of amenorrhea for a minimum of 24 months and a serum FSH (follicle-stimulating hormone) concentration of 25 mIU/mL (milli-International unit per milliliter) and negative pregnancy test.

Exclusion Criteria

• Current or prior use of medications known to affect bone (e.g. bisphosphonates, calcitonin, selective estrogen receptor modulators, denosumab, diphenylhydantoin, recent systemic glucocorticoid use), bone mineral density T score of less than -2.5 and greater than +2, Vitamin D level less then 12 ng/ml, BMI (body mass index) of greater than 32, current alcohol or drug abuse: more than 3 alcoholic beverages per day or current abuse of illicit drugs or prescription medication, uncontrolled or untreated cardiac or pulmonary disease liver disease: history of hepatitis or ALT (alanine aminotransferase) or AST (aspartate aminotransferase) greater than 2x ULN (upper limit of normal), renal disease: history of renal disease or serum creatinine greater than 2x ULN diabetes, pacemaker or metallic implants considered a contraindication to MR scanning.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Felix Wehrli

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Felix W Wehrli, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

3408455

Identifier Type: -

Identifier Source: org_study_id