SBIR-STTR Award

The goal of this project is to develop a biomarker - the Connective Tissue Motion Measure (CTMM) - quantifying the functional behavior of perimuscular connective tissues. The differential motion between specific connective tissue strata will be measured during tissue displacement (linear oscillation) initiated by a computer-controlled needle stimulus tool (NST). The CTMM will be suitable as an outcome measure for mechanistic and clinical studies of CAM interventions. The CTMM also will potentially serve as a clinical diagnostic and treatment-monitoring tool for manual therapists, acupuncturists, and CAM clinicians interested in assessing the functional status of a patient's connective tissue. Our Specific Aims are: Aim 1: Develop an integrated, user-friendly, and reliable system for conducting the CTMM. 1) Design and fabricate an automated Needle Stimulus Tool (NST) capable of providing a controlled displacement stimulus to the targeted connective tissue strata. 2) Integrating the NST with an ultrasound transducer in a clinically practical configuration allowing for the measurement and analysis of tissue displacement. 3) Preliminary validation of optimal CTMM procedures and data analysis techniques by performing the measure 1) in-vitro and 2) in-vivo in 5 human subjects. Milestones: Successful completion of Aim I of this work will be indicated by the following: 1. Completion of an operational NST device which is capable of achieving the target linear needle motion requirements. 2. Successful testing of the overall CTMM system demonstrating that the target needling accuracy requirements are achieved in-vitro, and in-vivo. Aim 2: Perform a pilot study of CTMM in human subjects with chronic low back pain (cLBP). Using optimal procedures determined in Aim 1c, we will test 17 subjects with chronic low back pain (cLBP) and 17 control subjects without cLBP. Milestone: Successful completion of Aim I of this work will be indicated by the following: Acquisition of preliminary data allowing sample size calculations for full-scale validation studies of the CTMM which will be conducted during Phase 2.

Public Health Relevance:
This project attempts to provide researchers and clinicians with a biomarker - the Connective Tissue Motion Measure - capable of documenting and monitoring the functional status of human connective tissues. Its purpose is to function as an outcome measure to monitor the effect of therapies that may have a therapeutic effect on connective tissue including manual therapies and yoga as well as acupuncture. It is anticipated that this technology will establish the usefulness of connective tissue motion measurements for the diagnosis and clinical management of chronic musculoskeletal pain in general, including low back pain.

Thesaurus Terms:
Acupuncture Procedure; After Care; After-Treatment; Aftercare; Analysis, Data; Back; Back Ache; Back Pain; Backache; Basic Research; Basic Science; Behavior; Biomechanics; Body Tissues; Chronic; Chronic Low Back Pain; Clinical; Clinical Management; Clinical Research; Clinical Study; Computers; Connective Tissue; Data; Data Analyses; Devices; Diagnosis; Diagnostic; Dorsum; Goals; Human; Human, General; In Vitro; Intervention; Intervention Strategies; Investigators; Link; Low Back Ache; Low Back Pain; Low Backache; Lumbago; Man (Taxonomy); Man, Modern; Manipulative Therapies; Manuals; Massage; Measurement; Measures; Methods; Methods And Techniques; Methods, Other; Monitor; Motion; Musculoskeletal Diseases; Musculoskeletal Pain; Needles; Outcome Measure; Patients; Phase; Physiologic; Physiological; Pilot Projects; Procedures; Research; Research Personnel; Researchers; Sample Size; Stimulus; System; System, Loinc Axis 4; Techniques; Technology; Testing; Therapeutic Effect; Therapy, Manipulation; Tissues; Translating; Translatings; Ultrasonic Transducer; Ultrasound Transducer; Universities; Validation; Vermont; Work; Yoga; Acupuncture; Biomarker; Chronic Pain; Chronic Painful Condition; Design; Designing; Functional Status; Human Subject; In Vivo; Innovate; Innovation; Innovative; Insight; Interest; Interventional Strategy; Language Translation; Massage Therapy; Musculoskeletal Disorder; Pilot Study; Public Health Relevance; Tool; User-Friendly; Validation Studies

Connective tissue dysfunction is emerging as a potentially important, and so far mostly overlooked, factor in the pathophysiology of chronic low back pain (LBP). We have developed and tested a novel instrument (StromaGlide) and test (Connective Tissue Motion Measure - CTMM) -quantifying the functional behavior of perimuscular connective tissues. The results of preliminary data strongly suggest that CTMM is reduced in chronic LBP. In this project, we plan to further test the performance of the CTMM as a biomarker in cross sectional and longitudinal studies of humans with and without LBP. We will also improve the commercial viability of the project by upgrading device components with less expensive (but equally well performing) FDA compliant subcomponents. Aim 1: Comparison of CTMM (test) in LBP vs No-LBP: We will follow up on the results of Phase 1 with a fully powered comparison of CTMM across 144 subjects, 72 with LBP and 72 with No-LBP. LBP and No-LBP groups will be frequency-matched for age, sex and BMI. In each subject, CTMM will be measured once bilaterally in the back. Based on our preliminary results, we hypothesize that CTMM will be reduced on average in the LBP group. Aim 2: Within-subject correlation of short term repeated CTMM: We will assess the stability of CTMM over repeated short term measurements. All LBP and No-LBP subjects tested in Aim 1 (N=144) will be re-tested one hour and one day following the initial test. We hypothesize that the CTMM will be reliable with an intra class correlation (ICC) greater than 0.8. Aim 3: Relationship of CTMM to clinical measures: All LBP subjects tested in Aim 1 (N=72) will also be evaluated with established measures of LBP symptoms and impairment. We hypothesize that CTMM will negatively correlate with the numeric pain index, McGill pain score, Oswestry disability index and functional measure score (50 foot walk, repeated sit-to-stand and repeated forward bend). All LBP subjects tested in Aim 1 (N=72) will also be retested 9 months and 15 months later along with repeated assessment of symptoms and impairment (target n=60;20% attrition allowance). We hypothesize that CTMM will be a significant time-varying covariate in predicting temporal changes in the functional and disability tests. Aim 4: Upgrade StromaGlide components to decrease manufacturing costs and adopt an FDA compliant design: We will substitute principal subsystems with low-cost, custom designed FDA compliant components suitable for commercialization. This will not alter device performance, rather it will reduce estimated manufacturing costs of these subsystems significantly. Upgraded device performance will be verified to match existing specifications.

Public Health Relevance:
The success of this project promises to improve the treatment of musculoskeletal disorders such as chronic idiopathic low back pain by providing an objective means for identifying connective tissue pathology. This would make a significant clinical impact by providing physicians, payers, and patients with much-needed information to improve the treatment of the large group of patients who suffer from costly chronic idiopathic musculoskeletal pain and dysfunction.