Effectiveness of Four Orthotic Insoles on Pain in the Lower Body Associated With Musculoskeletal Stress

Study Overview
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Brief Summary
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This was an open-label, single-centre, parallel-group clinical investigation, to evaluate the effectiveness and in-use tolerability of a range of four orthotic insoles on target areas of pain in the lower body, associated with musculoskeletal stress, experienced by those who spend most of their working day on their feet

Detailed Description
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This was an open-label, single-centre, parallel-group clinical investigation, to evaluate the effectiveness and in-use tolerability of a range of four orthotic insoles on target areas of pain in the lower body, associated with musculoskeletal stress, experienced by those who spend most of their working day on their feet. The investigation design included two periods; 'run-in' period and 'treatment' period. The treatment period comprised of two sub-periods; a 'breaking-in' period and the 'full use' period. The breaking-in period was intended to allow time for the subjects' feet to accustom to wearing the insoles. The full-use period was used to determine effectiveness of the insoles. These periods constitute lengths of time defined for the purpose of the investigation as working episodes. Working episodes were defined as at least 3 (up to 6) consecutive working days of at least 6 hours each at work, following at least 2 consecutive non-working days. Eligible subjects at Visit 1 (screening) were enrolled into the run-in period, where subjects were assessed prior to treatment with the insoles under investigation. During the run-in period, consisting of one working episode, subjects self-reported their pain without using insoles on a daily basis (Q3-9 of the Brief Pain Inventory (BPI)), in order to provide the baseline data to which the insoles were compared. Eligible subjects were enrolled into the treatment period at Visit 2 and assigned the insole relevant to the target pain area/pain area combination. Insole use was built up gradually during a breaking-in period, which constituted one working episode, with at least one nonworking day prior to the start of the working episode. Following the breaking-in period, the full-use period commenced. During the treatment period, subjects wore the insoles on working days and as much as possible on non-working days, self-reporting their pain daily (BPI Questions 3 - 9 inclusive).

Official Title
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An Open-label, Single-centre, Parallel-group Clinical Investigation, to Evaluate the Effectiveness and In-use Tolerability of a Range of Four Orthotic Insoles on Target Areas of Pain in the Lower Body, Associated With Musculoskeletal Stress, Experienced by Those Who Spend Most of Their Working Day on Their Feet

Conditions
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Musculoskeletal Pain

Intervention / Treatment
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* Device: Orthotic Insole: Lower Back
* Device: Orthotic Insole: Heel
* Device: Orthotic Insole: Knee to Heel
* Device: Orthotic Insole: Arch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Those who gave informed consent. Those who understood the purpose of the investigation, cooperate with the investigation procedures and tasks and were to attend the investigational site for all investigation assessments. Those were willing to continue with their normal daily activities, including any cosmetic foot care regimens (including the use of products) throughout the investigation and not partake in exercise which is not normal for them and which would be deemed by the Investigator to impact study assessments, or any new foot care or podiatric treatments unless agreed in advance with the Investigator. Those who wore the same or similar type of standard shoe during their working day/shift for at least the 4 weeks prior to enrolment (Visit 1) (or they have worn a different shoe which cause no change to their pain) and who were able to wear the same standard* shoe during their working day / shift for the duration of the investigation. Eligibility regarding this criterion was confirmed at Visit 1 but will also confirmed by the physiotherapist at Visit 2, following their assessment. *A standard shoe was defined as closed shoe, ≤2-inch heel, with an adequate sole, upper and toe box to accommodate the orthotic insole, as determined by the physiotherapist. Shoes with orthotic-type internal contouring (as determined by the physiotherapist to include features which could alter gait) or shoes with an arch support greater than 12 mm would not be permitted. Odour-eaters cannot be used during the treatment period. Male and female subjects from the age of 18 years and a BMI of 18.5-29.9 kg/m² inclusive. Those who had access to a mobile device (iOS or Android smart phone or tablet), with access to the internet, and are able to operate an app. Those with a shoe size between 4.5 to 11 (UK). Those who worked at least 30 hours per week which usually involved working episodes (defined as at least 3 (up to 6) consecutive working days (of at least 6 hours each at work) following at least 2 consecutive non-working days), which were expected to continue throughout their involvement in the investigation, and included at least 4 working episodes during the 4 (up to 5)-week treatment period. These working episodes should be non-complex in the opinion of the Investigator, to ensure continued eligibility. Those who spent most (at least three quarters) of their working day on their feet, and remained in their current employment/work environment throughout the investigation period. Those who have experienced pain associated with musculoskeletal stress during working episodes, for at least 4 weeks prior to enrolment (Visit 1) that they can distinguish as being in one of the following primary areas of pain or combination thereof, that the Investigator or designee considers could be treated with the relevant insole to be used in the investigation: Lower back Knee and/or Heel Arch Heel Eligibility regarding this criterion will also be confirmed by the physiotherapist at Visit 2, following their assessment. Those who scored an average of 5 (±1) on the BPI average pain item (question 5) over the first three consecutive working days of the run-in period working episode**, when assessed specifically in their primary target pain area/pain area combination, as confirmed at Visit 2. If the run-in period constituted more than one working episode (e.g. due to the scheduling of Visit 2), only the data from the first working episode was included in the calculation to determine eligibility, providing this included at least three consecutive working days. Otherwise data from the second working episode was used. Exclusion Criteria: Those who had a current medical condition that is contraindicated by the use of the orthotic insoles (e.g. peripheral vascular disease, sensory neuropathy or diabetes). Those who currently use prescribed orthotics for biomechanical or other issues, or have received and used prescribed orthotics within the last 12 months or over-the-counter (OTC) orthotics in the last 6 months (odour-eaters and any non-structured/non-orthotic shock-absorber insole were permitted). Those with any significant medical history which in the opinion of the Investigator could have interfered with the assessments of the investigation. For example; structural conditions (e.g. bunion or bunionette), lower limb or foot injury, rheumatic disease (e.g. rheumatoid arthritis, scleroderma, polymyalgia rheumatica), fibromyalgia, neurological disease or moderate to severe depression. Those who were taking any of the following medications: Anti-psychotic, sedatives, muscle-relaxants or medicines intended to treat neuropathic pain Anti-inflammatory medications which would reduce systemic inflammation or locally at the target pain areas (low dose Aspirin (75 mg daily) and nasal/inhaled steroids could have been considered acceptable, where in the opinion of the Investigator they would not interfere with the assessments of the investigation) An unstable dose of anti-depressants (defined as a change in therapy within the last 6 months). Those who are taking regular medication for targeted pain (including OTC pain relief, in excess of 2g paracetamol daily) which is either beyond the maximum recommended daily dose according to the SmPC or which the Investigator deems inappropriate for the subject to continue at the same dose throughout the investigation. Those who were pregnant or who had given birth within the past 6 months. Females of child-bearing potential who were unwilling to use a minimum of an acceptable (as defined by the Clinical Trials Facilitation Group (CFTG; 2014) recommendations) level of birth control, for the entire duration of the investigation. Suitable methods of birth control (in accordance with highly effective and acceptable methods of birth control defined by the CTFG) included: Combined (estrogen and progestogen containing) hormonal contraception associated with the inhibition of ovulation; oral, intravaginal, transdermal. Progestogen-only hormonal contraception associated with the inhibition of ovulation; oral, intravaginal, transdermal. Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action Male or female condom with or without spermicide Cap, diaphragm or sponge with spermicide Intrauterine device Intrauterine hormone-releasing system Bilateral tubal occlusion Vasectomised partner (where this was the subject's sole sexual partner and where the vasectomised partner had received medical assessment of the surgical success) Sexual abstinence (where the subject was willing to refrain from heterosexual intercourse during the entire period of the investigation in line with their preferred and usual lifestyle) Females who were considered to be of child-bearing potential were those who were fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause (Clinical Trials Facilitation Group, 2014). Those who suffered from allergies or sensitivities to the raw material of the insoles (as detailed in the Investigator Brochure). Those who had participated in another clinical investigation within the 3 months prior to enrolment into the run-in period. Employee at the investigational site, or a partner or first degree relative of the Investigator or member of the investigation team at the site. Those, in the opinion of the Investigator, who were not deemed suitable or were unable to comply fully with the investigation requirements, for any other reason.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An open-label, single-centre, parallel-group clinical investigation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Lower back pain associated with musculoskeletal stress<br>Subjects eligible for the study self selected the insole for the pain in-accordance with the pain that they were experiencing due to musculoskeletal stress. Subjects within this arm of the study experienced lower back pain; the subjects selection was corroborated by a physiotherapist. | Device: Orthotic Insole: Lower Back<br>* This Insole is a full-length shaped orthotic insole, with a heel cup and an arch support. The insole can cover several shoe sizes and can be cut to the correct size to fit in the shoe.<br>|
| Experimental: Experimental: Heel pain associated with musculoskeletal stress<br>Subjects eligible for the study self selected the insole for the pain in-accordance with the pain that they were experiencing due to musculoskeletal stress. Subjects within this arm of the study experienced pain in the heels of their feet; the subjects selection was corroborated by a physiotherapist. | Device: Orthotic Insole: Heel<br>* This Insole is a horseshoe shaped flexible heel cup with a softer area where the heel would be expected.<br>|
| Experimental: Experimental: Knee to Heel pain associated with musculoskeletal stress<br>Subjects eligible for the study self selected the insole for the pain in-accordance with the pain that they were experiencing due to musculoskeletal stress. Subjects within this arm of the study experienced Knee to Heel pain; the subjects selection was corroborated by a physiotherapist. | Device: Orthotic Insole: Knee to Heel<br>* This Insole is a ¾ length rigid orthotic insole with a softer area where the heel would be expected. Each insole will cover several shoe sizes.<br>|
| Experimental: Experimental: Arch pain associated with musculoskeletal stress<br>Subjects eligible for the study self selected the insole for the pain in-accordance with the pain that they were experiencing due to musculoskeletal stress. Subjects within this arm of the study experienced pain in the arch of their feet; the subjects selection was corroborated by a physiotherapist. | Device: Orthotic Insole: Arch<br>* This Insole is a ¾ length shaped medical device with a softer area incorporated into the ball of foot and heel area and an external arch. support and 6-8 mm metatarsal dome. The slim fit insole runs from the heel along under the arch of the foot and reaches to just behind the toes to prevent squashing the toes in tight fitting shoes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the pain relief caused by orthotic insoles on pain associated with musculoskeletal stress. Assessed though the change in pain, measured by the Brief Pain Inventory questionnaire score. (For each of the four orthotic insoles separately.) | The average change from baseline in the daily composite score of the worst, least, average and current pain, as measured by Questions 3-6 of the Brief Pain Inventory (BPI, scored on a scale of 0-10 with the lower number indicating less pain) when compared to the first three days of the last working episode. To account for differences in subjects working patterns a definition was created, a valid working episode was considered to be two non-working days followed by at least three and up to five working days. (this definition was used for all outcomes) The baseline was defined as the first three consecutive working days of baseline working episode (Days 0-3). The first three days of the last working episode could occur from Days 27-30 for subjects that worked 3 consecutive working days up to Days 44-47 for subjects that worked five consecutive working days For each of the four orthotic insoles separately. | Time frame is dependent on working pattern Days 0-5 compared to Days 44-47 and Days 0-3 compared to Days 27-30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the pain relief caused by orthotic insoles on pain associated with musculoskeletal stress over the first three days of each working episode. Assessed though change in pain, measured by the BPI. (For each of the four orthotic insoles) | The average change from baseline in the daily composite score of the worst, least, average and current pain, as measured by Questions 3-6 of the Brief Pain Inventory (BPI, scored on a scale of 0-10 with the lower number indicating less pain), during the first three consecutive working days of each working episode (WE) of the treatment period The baseline WE was defined as the first three consecutive working days of (Days 0-3): st WE- the first three days could occur from Days 12-15 for subjects that worked 3 consecutive working days up to Days 23-26 for subjects that worked five consecutive working days nd WE- the first three days could occur from Days 17-20 for subjects that worked 3 consecutive working days up to Days 30-33 for subjects that worked five consecutive working days rd WE- the first three days could occur from Days 22-25 for subjects that worked 3 consecutive working days up to Days 37-40 for subjects that worked five consecutive working days | Days 0-5 compared to Days 23-26, Days 30-33, Days 37-40, Days 0-3 compared to Day 12-15, Day 17-20, Day 22-25, Day 27-30 for subjects that worked 3 consecutive working days | 
| Evaluation of the pain relief caused by orthotic insoles on pain associated with musculoskeletal stress over each working episode. Assessed though change in pain, measured by the BPI questionnaire.(For each of the four orthotic insoles) | The change from baseline in the composite score of the worse, least, average and current pain, as measured by Questions 3-6 of the Brief Pain Inventory (BPI, scored on a scale of 0-10 with the lower number indicating less pain), completed at the end of each working episode (WE) of the treatment period. The baseline WE was defined as Days 0-3 or Days 0-5 depending on the working pattern of the subjects: st WE- the last working day could occur on Day 12-15 for subjects that worked 3 consecutive working days (CWD) up to Days 23-28 for subjects that worked 5 CWD nd WE- the last working day could occur on Day 17-20 for subjects that worked 3 CWD up to Day 30-35 for subjects that worked 5 CWD rd WE- the last working day of the 3rd working episode could occur from Day 22-25 for subjects that worked 3 CWD up to Day 37-42 for subjects that worked 5 CWD th WE- the last working day could occur from Day 27-30 for subjects that worked 3 CWD up to Day 44-49 for subjects that worked 5 CWD | Days 0-5 compared to Day 23-28, Day 30-35, Day 37-42, Day 44-49 for subjects that worked five consecutive working days, Days 0-3 compared to Day 12-15, Day 17-20, Day 22-25, Day 27-30 for subjects that worked 3 consecutive working days | 
| Proportion of subjects who achieve a change of ≥1 unit from baseline Assessed though the change in pain, measured by the Brief Pain Inventory questionnaire score. (For each of the four orthotic insoles separately.) | The overall proportion of subjects who achieve a change of ≥1 unit from baseline in the daily composite score of the worst, least, average and current pain, as measured by Questions 3-6 of the Brief Pain Inventory (BPI, scored on a scale of 0-10 with the lower number indicating less pain), during the first three consecutive working days of the last working episode of the treatment period. For each of the four orthotic insoles separately. To account for differences in subjects working patterns a definition was created, a valid working episode was considered to be two non-working days followed by at least three and up to five working days . The baseline was defined as the first three consecutive working days of baseline working episode (Days 0-3). The first three days of the last working episode could occur from Days 27-30 for subjects that worked 3 consecutive working days up to Days 44-47 for subjects that worked five consecutive working days | Days 0-5 compared to Days 44-47 for subjects that worked 5 consecutive working days, Days 0-3 compared to Days 27-30 for subjects that worked 3 consecutive working days | 
| Subject impression of change in pain (Visual Analogue Scale) (For each of the four orthotic insoles separately.) | Subjects' rating of overall improvement in pain since pre-treatment, completed at the end of the last working episode of the treatment period. For each of the four orthotic insoles separately. Scored on a scale of -3 to +3 with 0 indicating no change in pain, a positive number indicating an improvement and negative indicating an increase in the pain | Day 6 and Day 15 (Visit 1) compared to Day 31 and Day 50 depending on the subjects working pattern. | 
| Investigator impression of change in subjects' pain (Visual Analogue Scale) (For each of the four orthotic insoles separately.) | Investigator's rating of the subjects' overall improvement in pain since pre-treatment, completed following the end of the last working episode of the treatment period. For each of the four orthotic insoles separately. Scored on a scale of -3 to +3 with 0 indicating no change in pain, a positive number indicating an improvement and negative indicating an increase in the pain | Day 6 and Day 15 (Visit 1) compared to Day 31 and Day 50 depending on the subjects working pattern. | 
| Change in quality of life, associated with improvement pain as assessed by the Brief Pain Inventory questionnaire. (For each of the four orthotic insoles separately.) | The change from baseline in quality of life, associated with overall improvement in pain in the primary area of pain, assessed by the Brief Pain Inventory pain (BPI) interference scores (Question 9; composite (average) score), completed at the end of each working episode (WE) of the treatment period. The baseline WE was defined as Day 3 or Days 5 depending on the working pattern: st WE- occurred from Day 12-15 for subjects that worked 3 consecutive working days (CWD) up to Day 23-28 for subjects that worked 5 CWD nd working episode- occurred from Day 17-20 for subjects that worked 3 CWD up to Day 30-35 for subjects that worked 5 CDW rd working episode- occurred from Day 22-25 for subjects that worked 3 CWD up to Day 37-42 for subjects that worked five consecutive working days th working episode- occurred from Day 27-30 for subjects that worked 3 CWD up to Day 44-49 for subjects that worked 5 CWD The BPI question is a scale of 0-10 with the lower number indicating less pain | Day 5 compared to Day 23-28, Day 30-35, Days 37-42 Day 44-49 for subjects that worked 5 CWD or Day 3 compared to Day 12-15, Day 17-20, Day 22-25, Day 27-30 for subjects that worked 3 CWD | 
| Change in quality of life, associated with improvement in pain as assessed by the EQ-5D-5L (questionaire) (For each of the four orthotic insoles separately.) | Change from baseline in quality of life, associated with overall improvement in pain in the primary area of pain, assessed by the EQ-5D-5L, completed at the end of the last working episode of the treatment period. For each of the four orthotic insoles separately. The baseline was defined as the first three up to five consecutive working days of baseline working episode therefore in the context of this endpoint the baseline assessment would occur on Day 3 or Days 5 depending on the working pattern of the subjects. Compared to the responses at the end of last working episode which could occur from Day 30 for subjects that worked 3 consecutive working days up to Day 49 for subjects that worked five consecutive working days. The EuroQol-5 dimension-5 Level (EQ-5D-5L), is made up of 5 questions scored 1 to 5 from these questions an index is created with a range between zero and 1 with a zero being death and 1 being perfect quality of life. | Day 3 up to 5 compared to Day 49 for subjects that worked five consecutive working days or Day 30 for subjects that worked 3 consecutive working days | 
| Change in work productivity and activity as assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (For each of the four orthotic insoles separately.) | Change from baseline in work productivity and activity, assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP), completed at the end of last working episode of the treatment period. For each of the four orthotic insoles separately. The baseline was defined as the first 3 up to 5 consecutive working days (CWD) of baseline working episode therefore in the context of this endpoint the baseline assessment would occur on Day 3 or Days 5 depending on the working pattern of the subjects. Compared to the responses at the end of last working episode which could occur from Day 30 for subjects that worked 3 CWD up to Day 49 for subjects that worked 5 CWD. The WPAI:SHP six questions on the subjects productivity and activity Impairment. Questions comprised of information on employment, including hours at work, hours missed from work and reasons for work missed. As well as the effect that pain had on their daily activities. | Quality of life on Day 3 up to 5 compared to Day 49 for subjects that worked five consecutive working days or Day 30 for subjects that worked 3 consecutive working days | 
| Subject impression of change in their work productivity and activity. (Visual Analogue Scale) (For each of the four orthotic insoles separately.) | Subjects' rating of overall improvement in their quality of life and work productivity and activity since pre-treatment, completed at the end of the last working episode of the treatment period. For each of the four orthotic insoles separately. The last working day is therefore different for each subjects working pattern this could occur from Day 30 for subjects that worked 3 consecutive working days (CWD) up to Day 49 for subjects that worked 5 CWD. This assessment was scored on a scale of -3 to +3 with 0 indicating no change, a positive number indicating an improvement and negative indicating an increase in quality of life | Quality of life improvement assessed on Day 49 for subjects that worked five consecutive working days or Day 30 for subjects that worked 3 consecutive working days | 
| Investigator impression of change in quality of life (Visual Analogue Scale) (For each of the four orthotic insoles separately.) | Investigator's rating of the subjects' overall improvement in their quality of life since pre-treatment, following the end of the last working episode of the treatment period. For each of the four orthotic insoles separately. The last working day is therefore different for each subjects working pattern this could occur from Day 30 for subjects that worked 3 consecutive working days up to Day 49 for subjects that worked five consecutive working days. This assessment was scored on a scale of -3 to +3 with 0 indicating no change in quality of life, a positive number indicating an improvement and negative indicating an increase in quality of life | Quality of life improvement assessed on Day 49 for subjects that worked five consecutive working days or Day 30 for subjects that worked 3 consecutive working days | 
| Safety and tolerability of the device (For each of the four orthotic insoles separately.) | Overall proportion of subjects with AEs and adverse device effects (ADEs), i.e. the occurrence of one or more AEs/ADEs per subject. For each of the four orthotic insoles separately. | through to study completion, from point of informed consent (Day 1) up to Visit 3 (Day 50) |