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Carpal Tunnel SyndromeNCT03299361

Diffusion Tensor Imaging of the Median Nerve Before and After Carpal Tunnel Corticosteroid Injection in Patients With Carpal Tunnel Syndrome: Feasibility Study

An observational study of Carpal Tunnel Syndrome, run by Tri-Service General Hospital (TSGH).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Carpal tunnel syndrome (CTS) is the most common nerve compression disorder in the upper extremity. Therapy for carpal tunnel syndrome includes physical and occupational therapy, the use of splints and other local measures, and corticosteroid injection into the carpal tunnel. Read more about this study

Who is it for?
Any age
Conditions the study is for
Carpal Tunnel Syndrome
What is being tested?
Magnetic resonance image (MRI)
Type of treatment
Injection or infusion
How many people
12 participants
Where
No sites listed yet
Study dates
26 May 2016to 7 Mar 2017
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: 1. All patients had the clinical diagnosis supported by electrodiagnostic investigations. 2. All patients underwent US-guided corticosteroid injection of median nerve and received MR study before and after the injection.

Who may be able to join

  • clinical diagnosis of unilateral or bilateral CTS based on a standardized and validated diagnostic scale

Who cannot join

  • prior carpal tunnel release or contraindications to MRI

About this study

Carpal tunnel syndrome (CTS) is the most common nerve compression disorder in the upper extremity. Therapy for carpal tunnel syndrome includes physical and occupational therapy, the use of splints and other local measures, and corticosteroid injection into the carpal tunnel. When these measures fail, open surgical release is considered the next step. Although the main disadvantage of corticosteroid injection is that symptoms are often short-lived relief and partial relief, it may not provide a permanent solution, corticosteroid injections are chosen because of lower level of invasiveness, faster recovery, and ease of the technique.

Diffusion tensor magnetic resonance imaging (DTI) reveals tissue microstructure based on random movements of water molecules. The measured diffusion-weighted images are further analyzed for parameter images that describe different characteristics of diffusion: apparent diffusion coefficient (ADC) is an absolute measure of the strength of diffusion, and fractional anisotropy (FA) describes the asymmetry of the diffusion direction due to tissue structures. Because the axonal cell membrane and the myelin sheath in nerve fibers prevent diffusion in the direction which is perpendicular to their fascicles, resulting in the isotropy of the diffusion of water molecules being lost. DTI is the only method which can give an indirect view of the microstructure of nervous tissue in addition to the pathway of the fibers.

Read more

DTI has been applied to study peripheral nerves, to demonstrate the feasibility of the method and to study nerve entrapment in carpal tunnel syndrome (CTS). The previous studies have demonstrated a decrease in FA in patients with CTS compared to healthy volunteers. The DTI parameters of the median nerve have revealed significant increase of FA and decrease in ADC with complete symptom relief 6 months after carpal tunnel release. However, Hiltunen et al. have demonstrated a significant decrease in ADC but no alter in FA in patients received open carpal tunnel release 1 year later and felt complete symptoms relief. By means of open carpal tunnel release, follow-up recordings were made at least 6 months after the operation to ensure time for post-operative tissue recovery. As a result, the investigators still do not understand the relevance between the parameters of DTI to symptoms relief in CTS patients receiving conservative treatment.

Different from carpal tunnel release, steroid injections are popular technique for CTS treatment and are believed to reduce perineural inflammation or soft tissue swelling, and may stabilize the neural membrane, thus limiting the ephaptic transmission in ischemic nerve fibers which causes symptoms. Corticosteroid injections can provide a rapid symptom relief at 2 weeks follow up. However, there is no report addressing the relation of functional change of median nerve at several anatomic locations to the symptom relief of CTS. Here the investigators monitored, by means of DTI, median nerve integrity in CTS patients before and after corticosteroid injection. This information may help to explain the hypothesis regarding the effect of corticosteroid to the median nerve, to identify which anatomic location of median nerve relevant to the symptom relief of CTS after corticosteroid injection, and be useful for the clinical follow-up of patients with nerve entrapments following conservative treatment.

Read the detailed description

Study subjects This study was approved by the institutional research ethics board. Written informed consent was prospectively obtained from all study subjects. Twelve consecutive patients (nine females, three male; mean age, 56 years; range, 38 to 76 years) suffering from bilateral CTS referred for consideration of carpal tunnel steroid injection were prospectively recruited. Inclusion criteria consisted of a clinical diagnosis of unilateral or bilateral CTS based on a standardized and validated diagnostic scale. The degree of the entrapment ranged from mild to severe according to the American Association of Electrodiagnostic Medicine ratings: mild = slowing of sensory conduction velocity (<50 m/s), moderate = slowing of sensory conduction velocity (<50 m/s) and delayed motor distal latency (>4 ms), and severe = absence of sensory response. Exclusion criteria included prior carpal tunnel release or contraindications to MRI. All patients also had the clinical diagnosis supported by electrodiagnostic investigations.

Ultrasound needle guidance:

The US-guided injection procedure was performed in a standardized manner. The one-needle two-syringe technique with US guidance was used (1) one needle is used for anesthesia, hydrodissection, and intra-carpal tunnel injection; (2) the first syringe is used to anesthetize, hydrodissect, and dilate the intra-carpal tunnel space; and (3) the second syringe is used to inject the corticosteroid therapy into the new hydrodissected space. After hydrodissection, the empty lidocaine syringe was detached from the needle while still in the carpal tunnel, and a 3-ml syringe prefilled with 10 mg triamcinolone acetonide suspension was attached to the indwelling needle, and the treatment was slowly injected into the hydrodissected neutral space. The injections were performed in a standardized fashion by a musculoskeletal radiologist (Y.C.H.) with 13 years of experience in US.

MRI protocol Magnetic resonance images were acquired at 3.0 T (Discovery MR750, GE Healthcare, Milwaukee, WI, USA) using a 8-channel wrist coil (GE Healthcare, Gainesville, FL, USA). The coil was at the center of the magnet to maximize the magnetic-field homogeneity. The subject's hand was fixed with a plastic plate and Velcro tape to the coil to restrict movements; the subjects were examined in prone position.

For DTI, the investigators recorded non-diffusion-weighted b0 image and 15 diffusion gradient directions with b = 1,200 s/mm2 from 20 axial slices of 4 mm thickness. Slices were positioned to cover the whole carpal tunnel and in part the proximal and distal nerve. The two most proximal and distal slices were excluded from the analysis because of potential bias caused by the rapid decrease in homogeneity at the edge of the coil. Thus, the total proximal-distal range examined was 80 mm. The other imaging parameters were as follows: repetition time (TR) = 10,000 ms, echo time (TE) = 101 ms, number of averages = 3 (during post-processing), field of view (FOV) = 12 cm and matrix 100 × 80 pixels. The voxel size was thus 1.46 × 1.46 ×4 mm3.

In addition to DTI, the imaging protocol comprised the following MRI sequences:

  1. Axial T2-weighted fast spin echo (FSE): TR = 5,430 ms, TE = 88 ms, echo train length (ETL) = 16, FOV = 12 cm, matrix 224 × 256 pixels, phase FOV = 0.7, the same slice positions as in DTI.
  2. Axial T1-weighted fast spin echo (FSE): TR = 457 ms, TE = 11~33 ms, flip angle = 110°, FOV = 12 cm, matrix 384 × 256 pixels, phase FOV = 0.7, the same slice positions as in DTI.

Data collection:

The patients' medical records were reviewed by a neurologist (F.C.Y.). Routinely, the investigators recorded clinical data (including sex, age, and side of injection, and the effect of treatment. The satisfaction scale of patients was rated using a Likert scale: 5 = greatly satisfactory; 4 = some residual symptoms and satisfaction > 50%; 3 = some residual symptoms and satisfaction = 50% ; 2 = residual symptoms and satisfaction < 50%; 1= unsatisfactory. Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) is the most commonly used questionnaire for the measurement of the severity of symptoms and functional status with reproducibility, internal consistency, and validity in patients with CTS. The symptom severity subscale of BCTQ consists of 11 questions with scores from 1 point (mildest) to 5 points (most severe), and the functional status of BCTQ subscale is made up of 8 questions with scores from 1 point (no difficulty in activity) to 5 points (unable to perform the activity at all). Patients were seen in the subsequent clinical visit to determine outcomes. The investigators also recorded the decrement of BCTQ between the pre-injection and post-injection.

Data analysis Two investigators (Y.C.H., H.Y.C.) with experience in peripheral nerve imaging assessed the quality of the DTI source data. No case with visible motion artefacts was identified. Eddy current induced distortion occasionally appeared on the very proximal imaging planes, but did not affect the measurement regions. The DTI source data was post processed using the commercial post-processing workstation (GE Healthcare, ADW4.5). The investigators blinded to clinical data, side, and time point relative to steroid injection randomly performed all measurements. The same author performed a second blinded analysis of all acquired datasets after a 2-week period. Raw DTI data was initially reviewed with regard to image quality and occurrence of artefacts. After performing the GE Workspace imaging co-registration of EPI images for motion correction (through plane), DTI-based tractography (DTT) of the median nerve was performed. By defining at least two seed points, fibers passing in anterograde and retrograde direction followed a streamline algorithm and terminated if FA values were below 0.15 or if there were angle changes over 27°. The median nerve was visualized using at least three different attempts with two ROIs placed at different slice positions along the nerve (covering the entire imaged carpal tunnel). The 3D course of the nerve was tracked with DTT computed with the FACT algorithm (Fiber Assignment by Continuous Tracking).

Fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured bilaterally at each time point. FA and ADC were calculated from free-hand regions of interest (ROIs) placed in the center of the median nerve at three levels: at the level of the distal radioulnar joint (the most proximal slice where by the distal radio ulnar joint was visualized) and at the level of the flexor retinaculum (level of the pisiform). To avoid partial volume artifacts, care was taken to draw the ROIs slightly smaller than the cross-sectional area of the median nerve. The size of the ROIs depended on the cross-sectional area of the nerve and all ROIs were placed on one slice only. Anatomic reference images were used to identify the median nerve. The measurement of each parameter was repeated three times and the mean was calculated. Representative images are presented.

Regarding the assessment of DTT, the investigators determined the nerve fiber tractography by morphology. Four different nerve trajectory patterns were defined by Breitenseher et al.: (1) If there was no alteration of the peripheral nerve trajectories, the pattern was rated "continuous". (2) If the trajectories were continuous, but irregularly organized, peripheral nerve tractography result was rated "deranged" .(3) In cases where only some of the ulnar nerve trajectories were interrupted in one peripheral nerve segment, the finding was defined as "partially discontinuous ". (4) If there was a complete discontinuity of all trajectories and a "gap" on at least one plane, tractography was classified as "completely discontinuous". DTT images were evaluated by two readers (Y.C.H., G.S.H.) in consensus.

Being tested
Magnetic resonance image (MRI)
Keywords
Carpal tunnel syndrome, Corticosteroid, Diffusion tensor imaging, Injection, Magnetic resonance image, Ultrasound
Medical subject headings
Carpal Tunnel Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Magnetic resonance image (MRI)Other

    Diffusion tensor magnetic resonance imaging (DTI) of MRI reveals tissue microstructure based on random movements of water molecules. Here we monitored, by means of DTI, median nerve integrity in CTS patients before and after corticosteroid injection. This information may help to explain the hypothesis regarding the effect of corticosteroid to the median nerve, to identify which anatomic location of median nerve relevant to the symptom relief of CTS after corticosteroid injection, and be useful for the clinical follow-up of patients with nerve entrapments following conservative treatment.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Inter-scan change of DTI at baseline and 2 weeks after injection

    The DTI values for each wrist at baseline were compared to the DTI of the same wrist at 2 weeks in individual patients. DTI parameters: FA (numeric; unit free), ADC (numeric; unit: mm2/s), and DTT (morphology, unit free); BCTQ (numeric; unit free)

    Measured: February, 2017

  2. Correlation of Inter-scan change of DTI with symptoms relief

    The investigators determined the inter-scan correlation between increment of DTI parameters and the decrement of BCTQ. DTI parameters: FA (numeric; unit free), ADC (numeric; unit: mm2/s), and DTT (morphology, unit free); BCTQ (numeric; unit free)

    Measured: February, 2017

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2017
  2. Study start26 May 2016
  3. Primary completion31 Dec 2016
  4. Study completion7 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03299361
Sponsor's protocol ID
TSGHIRB 1-105-05-056
Status last verified
Sep 2017
First submitted
20 Sep 2017
Last updated
3 Oct 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Stevens JC, Sun S, Beard CM, O'Fallon WM, Kurland LT. Carpal tunnel syndrome in Rochester, Minnesota, 1961 to 1980. Neurology. 1988 Jan;38(1):134-8. doi: 10.1212/wnl.38.1.134.

    PubMed 3336444
  • Katz JN, Simmons BP. Clinical practice. Carpal tunnel syndrome. N Engl J Med. 2002 Jun 6;346(23):1807-12. doi: 10.1056/NEJMcp013018. No abstract available.

    PubMed 12050342
  • Gonzalez MH, Bylak J. Steroid injection and splinting in the treatment of carpal tunnel syndrome. Orthopedics. 2001 May;24(5):479-81. doi: 10.3928/0147-7447-20010501-16.

    PubMed 11379997
  • Jarvik JG, Comstock BA, Kliot M, Turner JA, Chan L, Heagerty PJ, Hollingworth W, Kerrigan CL, Deyo RA. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial. Lancet. 2009 Sep 26;374(9695):1074-81. doi: 10.1016/S0140-6736(09)61517-8.

    PubMed 19782873
  • Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J. 1994 Jan;66(1):259-67. doi: 10.1016/S0006-3495(94)80775-1.

    PubMed 8130344
  • Le Bihan D. Molecular diffusion, tissue microdynamics and microstructure. NMR Biomed. 1995 Nov-Dec;8(7-8):375-86. doi: 10.1002/nbm.1940080711.

    PubMed 8739274
  • Basser PJ, Jones DK. Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review. NMR Biomed. 2002 Nov-Dec;15(7-8):456-67. doi: 10.1002/nbm.783.

    PubMed 12489095
  • Basser PJ, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B. 1996 Jun;111(3):209-19. doi: 10.1006/jmrb.1996.0086.

    PubMed 8661285
  • Hiltunen J, Suortti T, Arvela S, Seppa M, Joensuu R, Hari R. Diffusion tensor imaging and tractography of distal peripheral nerves at 3 T. Clin Neurophysiol. 2005 Oct;116(10):2315-23. doi: 10.1016/j.clinph.2005.05.014.

    PubMed 16125460
  • Skorpil M, Karlsson M, Nordell A. Peripheral nerve diffusion tensor imaging. Magn Reson Imaging. 2004 Jun;22(5):743-5. doi: 10.1016/j.mri.2004.01.073.

    PubMed 15172070
  • Kabakci N, Gurses B, Firat Z, Bayram A, Ulug AM, Kovanlikaya A, Kovanlikaya I. Diffusion tensor imaging and tractography of median nerve: normative diffusion values. AJR Am J Roentgenol. 2007 Oct;189(4):923-7. doi: 10.2214/AJR.07.2423.

    PubMed 17885066
  • Khalil C, Hancart C, Le Thuc V, Chantelot C, Chechin D, Cotten A. Diffusion tensor imaging and tractography of the median nerve in carpal tunnel syndrome: preliminary results. Eur Radiol. 2008 Oct;18(10):2283-91. doi: 10.1007/s00330-008-0971-4. Epub 2008 Apr 17.

    PubMed 18418602

Questions about this trial

What is this clinical trial studying?

An observational study of Carpal Tunnel Syndrome, run by Tri-Service General Hospital (TSGH).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Inter-scan change of DTI at baseline and 2 weeks after injection (time frame: February, 2017). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03299361, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2017.

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