Studie

Clinical Study: Scientific Publication in Malang Neurology Journal Edition 01/2019

Final / Closing Report

ABSTRACT 

Background: The present study was conducted with an aim to compare the efficacy and safety of CarpaStretch® relative to wrist splinting in patients with CTS. 

Objective: To examine the effect of using CarpaStretch®, a novel dynamic splint for the treatment of  Carpal Tunnel Syndrome. 

Methods: The efficacy and safety of CarpaStretch® was compared with conventional splints in a  prospective 6-month trial with a follow-up at 12 months. 30 subjects with confirmed Carpal Tunnel  Syndrome were enrolled in each group. Nerve conduction tests, wrist MRI, provocation tests and  patient satisfaction questionnaires were assessed in the study. 

Results: At the end of 6 months, there were significant increases in sensory nerve conduction velocity  in both intervention and control groups, and the difference between groups were not significant. A  higher proportion of subjects using CarpaStretch® showed improvement in severity grade relative to  control at 6 months. Small but clinically meaningful increases were seen in carpal tunnel dimensions  in the CarpaStretch® group. There was a greater reduction in the incidence of paraesthesia and  increase in the time of paraesthesia in the CarpaStretch® group. No adverse effects were reported in  either group, but 4 subjects in the control group opted for surgery. 

Conclusion: CarpaStretch® can be used for effective non-surgical management of Carpal Tunnel  Syndrome. 

Keywords: CTS, CarpaStretch®, MRI, NCV 

Introduction 

Carpal Tunnel Syndrome (CTS) is a common condition  affecting up to 5% of the population,1 and is caused by the  compression of the median nerve at the wrist in the carpal  tunnel.2 The common symptoms are numbness, tingling and  pain over the areas supplied by the nerve, which include the  thumb, index finger, middle finger and radial part of the  ring finger.3,4 CTS causes a loss in the working capability  and hence can have a significant economic impact on an  individual’s life. Blue-collar workers and housewives have  an increased risk of CTS.5 

Moreover, manual labor, exposure to vibratory tools and  repetitive flexion and extension of the wrist combined with  gripping are known risk factors for CTS but the risk from  using a computer mouse or keyboard is unclear.6,7,8 There  are several conservative treatment options such as oral  medications, corticosteroid injections and wrist splinting,  but their success varies in individual cases.1 Carlson et al.,  (2010)3 have discussed non-surgical management methods  for CTS such as bracing, injections, hand/occupational  therapy, exercise and other alternative therapies viz., laser,  acupuncture, magnetic field therapy and yoga, while Smith 

et al., (2004)9 have reviewed systemic management  methods for CTS. CarpaStretch® is a newly developed  device for the non-surgical management of CTS using  mechanical means. The CarpaStretch® splint stretches the  transverse carpal ligament utilizing the proven principles of  low-load, prolonged-duration stretch (LLPS), which causes  an increase in the lumen of the carpal tunnel. This relieves  the pressure on the compressed median nerve and is  expected to provide relief to the symptoms of CTS. This  was attributed to the prolonged duration of stretching  employed by the dynamic splinting system.2,10,11,12,13,14  The  theory behind the “low-load, prolonged stretching”  employed in dynamic splinting originates with the coiled  structure of collagen (the primary component in connective  tissue). Prolonged stretching at the end-range of motion  allows the protein polypeptide binds to realign on the coiled  collagen triple helix molecules, thereby elongating the  connective tissue. This modality has been shown to be  effective in contracture reduction, but analysis in a larger  population was recommended. The purpose of this study  was to examine the effect of dynamic splinting on 60  patients diagnosed with CTS. 

The present study was conducted with an aim to compare  the efficacy and safety of CarpaStretch® relative to wrist  splinting in patients with CTS. If CarpaStretch® were to  increase the lumen of the carpal tunnel and relieve the  pressure onthe median nerve, the changes could be  expected are increase in sensory nerve conduction velocity,  decrease in paraesthesia by Phalen’s and Tinel’s tests,  increase in time to paraesthesia, increase in dimensions of  the carpal tunnel, median nerve by MRI and overall  improvement in the quality of life of patients. 

Methods 

The trial was a randomized, open label, controlled, parallel- group, prospective study. Ethical approval was obtained  from the Institutional Ethics Committee of Jehangir Clinical  Development      Centre    (Registration        No.  ECR/352/tnst/MW2013/RR-16) which is accredited by the  Association for the Accreditation of Human Research  Protection Program (AAHRPP) and National Accreditation  Board for Hospitals and Health Care Providers (NABH)  (Certificate No. EC-CT-2018-0023). The study subjects  were recruited from Jehangir Hospital, Pune, India between  March 2015 to July 2016. Patients aged 18-80 years who  were diagnosed with CTS by antidromic Nerve Conduction  Velocity Test (NCV) were eligible for the study. Patients  who had any previous surgery on the affected wrist, trauma  to the affected hand that required surgery or immobilization  in the previous 12 months, neurological deficit (motor), or  any chronic disorder or severe disease were not considered  for study participation. 

Subjects were randomized in 1:1 allocation ratio using  simple randomization to receive the interventional  CarpaStretch® or the control treatment. The intervention  group was provided with CarpaStretch® to be worn on the  affected wrist. The control group received the standard of  care which included exercise, a wrist splint and/or NSAIDs  as prescribed by the investigator. The treatments were  continued for a period of six months with a follow-up of  another six months.  

CarpaStretch® 

The investigational device CarpaStretch® has two  components: 

Stretching device which is made up of an elastic band (91%  viscose/ 9% elastodien), Velour Pads (100% polyamide),  elastic foam (100% silicon), well-loc (polyester/  polypropylene), and a liner (87% polyamide/ 13%  elastomer). 

Two self-adhesive, hypoallergenic pads which have an  acrylate based latex free coat on one side (which is in direct  contact with the skin). On the upper surface of the adhesive  pads, a Velcro pad is provided. The adhesive pads allow a  consistent and accurate transmission of the expansion force  from a corresponding expansion mechanism. The elastic  stretching device allows adjustment of the force applied.  The adhesive pads are disposable and can be replaced with  new ones when soiled or become loose. The CarpaStretch®  device is shown in Figure 1. 

Method of Use 

The two adhesive pads are to be removed from the packing and  one is to be stuck to thenar eminence and other to hypothenar  eminence, distal to flexor wrist crease. The space between the two pads should be equal to the thickness of the little finger. One end  of the stretching device should be stuck to the thenar pad by  inserting the thumb in the hole and the device wrapped around the  palm dorsally and with the other end stuck to the hypothenar pad.  A foam pad (100% silicon) on the stretching device on the dorsal  surface of the palm is the main element for applying pressure on  the surface of bone. In the study, the device was initially worn  daily for one hour. It was increased weekly by one hour up to four  weeks and not used at night. After four weeks, it was  recommended for use during the night for as long as tolerated, but  daytime use for at least four hours was continued till 6 months.

Mechanism of Action 

Low-load, prolonged-duration stretch is the gradual application of  tension over time to the connective tissue in a joint, producing a  permanent remodelling of the soft tissue. The CarpaStretch® splint  stretches the transverse carpal ligament utilizing the proven  principles of low-load, prolonged-duration stretch and three point  principle used in splint. The detailed mechanism of action is  shown in Figure 2. 

Measurements Nerve Conduction Test 

The wrist joint of the patients was scanned using RMS  EMG EP MK2 System (Model No.F2MG2AB5D116). The  surface electrode which is an active electrode was held on  abductor pollicis brevis and was stimulated 3 cm proximal  to the wrist crease giving distal motor latency of the median  nerve. Sensory nerve conduction study of the median nerve  was done by orthodromic stimulation of second digit and  recording from median nerve at the wrist. This was done by  placing an electrode near the base of the ring finger  following which the median nerve was stimulated  approximately 13 cm proximal to the recording electrode. 

The measurements were recorded at baseline, after 6  months of treatment and at the 12 month follow-up. 

Data with missing nerve conduction test values at 6 months  and 12 months was deleted from the analysis. Nerve  conduction test zero values occurring during the study were  actually not zero values or missing but rather high severity  cases the values were too low to be measured. If basal  values were zero but subsequent values non zero, then these  basal zero values were replaced by minimum valueof 11.5  m/s for statistical analysis. Zero or missing values of nerve  conduction test at 6 month or 1 year were replaced by the  values obtained by regression method to avoid loss of data.

Wrist MRI 

The wrist joint of the patients was scanned using 3.0 Tesla  MRI Super conducting System (Ingenia Release 5, Philips  Healthcare, Amsterdam, Netherlands). An axial plane was  used and axial T2 and PDF sequences were obtained. The  Scan was of 7.5 cms field of view, slice thickness was 3  mm with 10% inter slice gap. AP and transverse diameters  of the carpal tunnel were measured at the level of pisiform  bone. The median nerves measurements were also obtained  at the same level in the form of AP and transverse  diameters. Additional incidental and clinically relevant  findings (ganglion cysts, associated ligament tears,  effusions, bony abnormalities) were separately noted. The  reporting of all the MRI scans was done by the same radiologist at baseline and after 6 months of treatment.  

Provocation Tests 

Phalen’s and Tinel’s tests15 were performed at baseline and  at 3, 6, 9 and 12 months. In Phalen’s test, patients were  asked to flex their wrist 90 degrees and keep it in that  position for 60 seconds. A response was considered positive  is if it led to paraesthesia along the distribution of the  median nerve. Tinel’s test was performed by tapping over  the volar surface of the wrist distal to proximal of FR. A  response was considered positive if it caused paraesthesia  in the innervated fingers.

Patients’ Satisfaction 

The Boston Carpal Tunnel Syndrome Questionnaire  (BCTSQ) is a specific, validated tool used extensively for  the assessment of CTS.16 This was used in conjunction with  the WHO Quality of Life (WHO-QOL) scale to measure  the impact of the treatment on the subject. These scales  were administered at baseline and at 3, 6, 9 and 12 months.  Any subject not satisfied with the treatment was allowed to  opt for surgery.

Statistical Methods Sample Size 

The sample size of the study was computed by taking cure  rate of 83% in Intervention group and 40% in Control  group and the end of 12 months. SAS 9.2 computer  package was used to calculate sample size. Fisher's exact  probability test computed sample size of 30 in each group  for 90% power.  

Statistical Analysis 

The primary endpoint of change from baseline in sensory  nerve conduction velocity (NCV) was analysed for the  treatment groups at 6 and 12 months. The proportion of  subjects with change in severity of CTS was computed. The  change in carpal tunnel diameters in wrist MRI was  assessed at 6 months. From the BCTSQ, the symptom severity and function status scores were computed and the  change from baseline was summarized at 3, 6, 9 and 12  months. Change in provocation tests (Phalen’s and Tinel’s  test) and quality of life using WHO-QOL were also  analysed at 3, 6, 9 and 12 months. Percentage of subjects  referred for surgery was computed. Data analysis was  performed using SPSS 15.0 (Statistical Package for Social  Sciences Version 15.0). 

Results 

Of the 60 subjects randomized in the study, 45 (75%)  completed 6 months and 37 (60%) completed the 12-month  follow-up. The mean age of the subjects was 48.3 (±12.8)  years and 82% were female. Demographic and baseline  characteristics of the treatment groups are summarized in Table 1 (see pdf).

Results of the nerve conduction tests (Table 2a) showed  significant increases in sensory NCV at 6 months and at 1  year for intervention group as well as for control group.  Increase in sensory NCV in Intervention group was 8.43  m/s which was highly significant (P<0.01) as compared to  Basal value. There was increase of 7.30 m/s in Control  group which was also significant (P<0.05). There was no  significant difference between increase in Intervention  Group and Control at 6 months. 

Similarly increase in sensory NCV in Intervention group at  1 year was 10.13 m/s which was statistically significant  (P<0.01) as compared to Basal value. There was significant  increase of 8.66  m/s  in Control group as compared to  Basal at 1 year which was significant (P<0.05). Comparison  of increase in NCV between Intervention and Control group  (Table 2b) indicated that the increase at 6 months and at 1 year was similar (no significant difference) between  Intervention Group and Control group. 

Improvement in severity of CTS is denoted as a reduction  of at least one point in severity grading. The proportion of subjects who had an improvement in CTS severity (Table  3) after 6 months of treatment was higher in the  intervention group relative to control at 6 months and at one  year. This difference was statistically significant by Chi  square test at 6 months and 1 year concluding that  Intervention had cured significantly more number of  subjects than Control group.

The Phalen’s test (Table 5) showed a significant reduction in both treatment groups in the proportion of subjects who  experienced paraesthesia. The reductions were significantly  larger (P=0.024) in the intervention group than in the  control group at Month 12. In both groups, there was a  significant increase in the time to paraesthesia, but the  between-group differences were not significant. Results  from Tinel’s test (Table 5) are similar to that of Phalen’s  test, with significant reductions in both treatment groups in  the incidence of paraesthesia. 

Both treatment groups had significant improvements in  symptom severity and functional status of the BCTSQ  (Table 6) at all-time points in the study. The between-group  differences in BCTSQ were not statistically significant.  Analysis of the WHO-QOL scores (Table 7) showed a  significant improvement in physical domain at 6 months in  the intervention group. The control group had no  statistically significant improvement at any time point in  the study.  

No adverse effects were observed in either group, but 4  subjects from the control group and none from the  intervention group opted for surgery. 

Discussion

The purpose of this prospective study was to examine the effect of CarpaStretch® on 60 patients diagnosed with CTS. The success of this treatment modality is hypothesized to be derived from prolonged, end-range stretching of the transverse palmar carpal ligament and the flexor retinaculum, because contracture of these structures contributes to compression in CTS. Dynamic tension and prolonged stretching have been successful in contracture reduction from head to toe, trismus14 to hallux rigidus.12 The low-load, prolonged duration of end-range stretching is hypothesized to be responsible for elongation of the connective tissue. Unlike traditional "positioning splints" which are simply designed to prevent the patient from aggravating their CTS condition, the patients treated with the dynamic splint are instructed to simply rest the device on their lap during the treatment periods for a cumulative time of 60 minutes per day. This paper showed that the new modality was effective in reducing symptoms and improving function in patients diagnosed with CTS. This study is also an answer to recommendations for further investigation of non-surgical treatments for CTS.2,17-23 This was the first hospital based randomized trial of CarpaStretch® device compared with the conventional wrist splint for patients with CTS. During the 6 months of the study, and the 12-month follow-up, the anatomical and functional changes noted may be increase in sensory NCV and improvement in CTS severity at 6 months, small but clinically meaningful improvements in carpal tunnel transverse diameters (median nerve, bony proximal and soft tissue) at 6 months, reduced incidence and increased time to paraesthesia over 12 months, improved Boston Carpal
Tunnel Syndrome Questionnaire and WHO-QOL (physical domain) scores over 12 months. These changes were seen consistently in the intervention group and less frequently in the control group. There were no adverse events associated with its use. This suggests that CarpaStretch® is safe for use. In addition, CarpaStretch® is simpler to use, and so is expected to be of greater benefit to patients over methods like splinting.
Many interventional studies have reported the comparison of the effects of different therapies for the treatment of CTS (YOGA therapy vs splint, splint vs surgery, surgery vs steroid. Yoga and surgical interventions were found to be effective.
Uchiyama et al., (2005)24 who studied quantitative MRI of the wrist and nerve conduction found that severity of the disease could be judged by evaluating not only longitudinal changes of signal intensity, and configuration of the median nerve, but also palmar bowing of the Transverse Carpal Ligament (TCL) and this was found to be associated with an increase in the area of the carpal tunnel. International Guidelines for CTS (2017)1 presently recommend only splint and surgery as methods of treatment (Lim et al., 2017), due to which the present results become clinically important. Berner (2008) et al,18 reported that CTS is treated with dynasplint and C-TRAC but results were assessed on the basis of symptom relief. This is first study to explore an effect of this device on carpal tunnel. Sucher et al, 200526 observed increase in the length of the transverse carpal ligament after doing manipulative treatment and along with dynamic orthosis should be more effective.
This study is the first to explore the effect of this nonsurgical intervention in Indians. Most intervention studies on CTS have used NCV and provocation tests. But our study also includes MRI of the wrist and subjective
improvement, as well as quality of life of the patient. Being an interventional study, the authors were able to compare the change in MRI measurements over a period of six months. However, the MRI was not done at the 12 month follow-up, so the authors could not observe if the improvements attained with CarpaStretch® at 6 months would have continued up to 12 months. There has been only one study in the past which measured multiple
parameters to assess prognosis in CTS.27,28 There are many parameters to assess the efficacy of CTS treatments. The present study demonstrates that CarpaStretch® affects some of these parameters, while establishing statistical superiority of the device over conventional wrist splint treatment in a few of these parameters. It is worth mentioning that 4 subjects in the control group, but none in the intervention group were referred for surgery, although the intervention group had more severe subjects at baseline. Further studies would establish the advantages of the device more conclusively and provide evidence for the mechanism of action that has been proposed. Though the intervention group showed significant improvement in some WHO-QOL parameters, it should be noted that 77% of the subjects in this group had bilateral CTS and only one arm was selected for treatment with CarpaStretch®. Hence the results of the WHO-QOL tests should be interpreted with some caution. Still, the improvement in these scores in the intervention group may be attributed to the user-friendliness of the device. It can be used through the day and is easy to apply and remove. It also eliminates the need for corticosteroid injections which are known to cause pain and other adverse reactions. Overall, CarpaStretch® proves to be a better treatment option, though the authors cannot deny that conventional therapy is also effective.