Apophysitis; Juvenile
Conditions
Brief summary
The goal of this clinical research study is to determine if there is a difference in time to meet return to sport criteria for Pediatric patients with apophysitis of the knee who receive iontophoresis with Dexamethasone Sodium Phosphate (DSP) and Physical Therapy (PT) as those who receive iontophoresis with placebo and PT or PT alone. Approximately 147 patients will be enrolled in this study.
Detailed description
Iontophoresis is a treatment that allows medication to be delivered across your skin to the painful area without having to have an injection into your muscle or soft tissue, through a vein in your arm, or taking a pill. Instead, liquid medication is placed on a patch (like a large Band-Aid) and then placed on your knee over the location where it hurts. A plastic device, like a battery, is then attached to the patch for three minutes. During this time, this device begins to deliver the medication through your skin and into the area that hurts, and also charges the patch so it can continue to deliver the medication for two hours once the device is removed. The medication is delivered by a mild electrical current. The most common drug used with iontophoresis for pain caused by such things as apophysitis of the knee is dexamethasone sodium phosphate (dexamethasone). This is an investigational study. Dexamethasone is a steroid medication that has been approved by the U.S Food and Drug Administration (FDA) to treat many types of problems (such as joint problems, skin and allergy problems, eye, stomach, and lung problems), but has not been approved to treat apophysitis of the knee using iontophoresis. In this study, it is an experimental drug. Participants will be randomized to one of three treatment groups: * Physical therapy with iontophoresis using Dexamethasone * Physical therapy with iontophoresis using an inactive drug called a placebo * Physical therapy alone Participants will be asked to attend study visits twice/week for up to 8 weeks or until they are able to pass the Return To Sport Checklist, whichever is sooner. Participants will the receive a 30-Day Follow Up phone call and complete a survey at the 90-Day mark, making each participant's study duration approximately five (5) months.
Interventions
DRUGDexamethasone Sodium Phosphate
Dexamethasone sodium phosphate administered via iontophoresis
PROCEDUREIontophoresis
Iontophoresis on affected knee
PROCEDUREPhysical Therapy
Physical therapy of affected knee
Sponsors
Children's Health System, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Written approval from the referring physician for potential subject to be considered for enrollment into this study 2. Provision of signed and dated informed consent form 3. Stated willingness to comply with all study procedures and availability for the duration of the study 4. In good general health as evidenced by written approval from referring physician for potential inclusion in study. 5. Has the ability to effectively identify pain/burns and communicate with the investigators or their parents that they are experiencing pain or burning during treatment 6. Referred to CHKD Sports Medicine PT by CHKD Primary Care Sports Medicine physicians or CHKD Orthopedics physicians with a diagnosis of apophysitis of the knee and with a prescription for standard PT treatment with iontophoresis 7. Able and willing to complete iontophoresis treatments within eight (8) weeks of first treatment 8. Must be ambulatory 9. Males 7 to 14 years of age who have not reached skeletal maturity (skeletal maturity based on referring physician's clinical judgement or as demonstrated via radiograph images taken within 90 days of enrollment) 10. Females 7 to 14 years of age who have not reached skeletal maturity (skeletal maturity based on referring physician's clinical judgement or as demonstrated via radiograph images taken within 90 days of enrollment) and who meet one of the following criteria: 1. Pre-menarcheal 2. Within two (2) year post onset of menses 11. Males or females over the age of 14 only with radiographic evidence of skeletal immaturity, with images taken within 90 days of enrollment 12. Index knee symptomatic for pain with activities of daily living or while playing sports.
Exclusion criteria
1. Index knee symptomatic for pain only with palpation and not with activities of daily living or while playing sport 2. Diagnosis of bilateral apophysitis of the knee where both knees meet all of the inclusion criteria 3. Systemic fungal infections 4. Has an implanted electronic device 5. Has a known sensitivity to DSP 6. Presence of damaged skin, denuded skin, or other recent scar tissue on index knee 7. Presence of active dermatologic conditions in the affected area (e.g., eczema, psoriasis) 8. Presence of an abnormal neurological exam that indicates the subject would have a reduced ability to perceive pain (e.g. peripheral neuropathy) 9. Has a known sensitivity to electrical current 10. Is currently taking systemic steroids 11. Has had iontophoresis with DSP treatment within the past 30 days 12. Previously enrolled in this study 13. Currently enrolled in another treatment research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Outcome as Measured in Length of Time to Meet Return To Sport Criteria (Measured in Days) | Measured at each Study Treatment Visit for a maximum of 12 Study Treatment Visits over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner | The Return To Sport Criteria is met when all items on the Return To Sport Checklist can be successfully achieved. There are no units of measure for any of the criteria listed as they are either achieved/passed or not achieved/failed based on the criteria listed. Once all criteria can be passed, this date is noted. The number of days from Visit 1 to the date when all criteria are achieved is calculated. This outcome is measured in days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Reported Outcome - Percent Difficulty With Activities as Measured by the Lower Extremity Function Scale (LEFS) | Collected at final visit, which is at Visit 12, maximum of 8 weeks, or when Return to Sport Criteria are met, whichever is sooner | The LEFS is a patient reported questionnaire that measures difficult of completing 20 activities. The maximum possible score of the LEFS is 80 points, indicating very high function. The minimum possible score is 0 points, indicating very low function. The LEFS data is reported as a percentage, calculated as XX points/80 \* 100. |
| Patient Reported Outcome - Activity Level as Measured by the Godin Leisure-Time Activity Questionnaire | Measured at Study Treatment Visit 1 to establish baseline activity level (prior to onset of injury/pain) | The Godin Leisure-Time Activity Questionnaire measures physical activity. Scores of 24 and above indicate the individual is Active, scores of 14-23 indicate the individual is Moderately Active, and scores of 14 and below indicate the individual is insufficiently active/sedentary. A higher score indicates higher levels of physical activity at baseline, thus would be considered a better outcome. The minimum possible score is 0, and there is no defined maximum score, as scores are based on patient's self-reported quantitative activity level, but scores of 24 and above indicate the highest levels of physical activity. |
| Patient Reported Outcome - Pain as Measured by the Wong-Baker FACES Pain Rating Scale | Collected at final visit, which is at Visit 12, maximum of 8 weeks, or when Return to Sport Criteria are met, whichever is sooner | This scale was created for children to help them communicate their pain. The scale shows a series of faces ranging from a happy face at 0, No hurt to a crying face at 10 Hurts worst. |
| Number of Participants With Adverse Events | Measured at each Study Treatment Visit (up to 12 Study Treatment Visits over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner), then again 2 - 3 days, 30 days, and 90 days after Return To Sport Criteria are met. | All adverse events that occur during participation in this research study, whether or not considered intervention-related, will be collected. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iontophoresis With Dexamethasone Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits.
Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis
Iontophoresis: Iontophoresis on affected knee
Physical Therapy: Physical therapy of affected knee | 16 |
| Iontophoresis With Sodium Chloride Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits.
Iontophoresis: Iontophoresis on affected knee
Physical Therapy: Physical therapy of affected knee | 15 |
| Physical Therapy Alone Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits.
Physical Therapy: Physical therapy of affected knee | 14 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 4 |
Baseline characteristics
| Characteristic | Iontophoresis With Dexamethasone | Iontophoresis With Sodium Chloride | Physical Therapy Alone | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 15 Participants | 14 Participants | 45 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 11 Participants | 8 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 14 / 16 | 10 / 15 | 9 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 | 0 / 14 |
Outcome results
Primary
Functional Outcome as Measured in Length of Time to Meet Return To Sport Criteria (Measured in Days)
The Return To Sport Criteria is met when all items on the Return To Sport Checklist can be successfully achieved. There are no units of measure for any of the criteria listed as they are either achieved/passed or not achieved/failed based on the criteria listed. Once all criteria can be passed, this date is noted. The number of days from Visit 1 to the date when all criteria are achieved is calculated. This outcome is measured in days.
Time frame: Measured at each Study Treatment Visit for a maximum of 12 Study Treatment Visits over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner
Population: Analysis of return to sport time in patients who met return to sport criteria during study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iontophoresis With Dexamethasone | Functional Outcome as Measured in Length of Time to Meet Return To Sport Criteria (Measured in Days) | 38.1 days to meet return to sport criteria | Standard Deviation 9.48 |
| Iontophoresis With Sodium Chloride | Functional Outcome as Measured in Length of Time to Meet Return To Sport Criteria (Measured in Days) | 30.2 days to meet return to sport criteria | Standard Deviation 6.8 |
| Physical Therapy Alone | Functional Outcome as Measured in Length of Time to Meet Return To Sport Criteria (Measured in Days) | 37.25 days to meet return to sport criteria | Standard Deviation 3.86 |
p-value: 0.036695% CI: [1.073, 9.005]Cox proportional hazards analysis
p-value: 0.023295% CI: [1.215, 14.273]Cox proportional hazards analysis
p-value: 0.6495% CI: [0.389, 4.615]Cox proportional hazards analysis
Secondary
Number of Participants With Adverse Events
All adverse events that occur during participation in this research study, whether or not considered intervention-related, will be collected.
Time frame: Measured at each Study Treatment Visit (up to 12 Study Treatment Visits over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner), then again 2 - 3 days, 30 days, and 90 days after Return To Sport Criteria are met.
Population: Participants in each group who experienced an AE
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Iontophoresis With Dexamethasone | Number of Participants With Adverse Events | Moderate | 4 Participants |
| Iontophoresis With Dexamethasone | Number of Participants With Adverse Events | Mild AE | 8 Participants |
| Iontophoresis With Dexamethasone | Number of Participants With Adverse Events | Severe | 2 Participants |
| Iontophoresis With Sodium Chloride | Number of Participants With Adverse Events | Moderate | 5 Participants |
| Iontophoresis With Sodium Chloride | Number of Participants With Adverse Events | Mild AE | 5 Participants |
| Iontophoresis With Sodium Chloride | Number of Participants With Adverse Events | Severe | 0 Participants |
| Physical Therapy Alone | Number of Participants With Adverse Events | Mild AE | 4 Participants |
| Physical Therapy Alone | Number of Participants With Adverse Events | Severe | 0 Participants |
| Physical Therapy Alone | Number of Participants With Adverse Events | Moderate | 5 Participants |
p-value: 0.57ANOVA
Secondary
Patient Reported Outcome - Activity Level as Measured by the Godin Leisure-Time Activity Questionnaire
The Godin Leisure-Time Activity Questionnaire measures physical activity. Scores of 24 and above indicate the individual is Active, scores of 14-23 indicate the individual is Moderately Active, and scores of 14 and below indicate the individual is insufficiently active/sedentary. A higher score indicates higher levels of physical activity at baseline, thus would be considered a better outcome. The minimum possible score is 0, and there is no defined maximum score, as scores are based on patient's self-reported quantitative activity level, but scores of 24 and above indicate the highest levels of physical activity.
Time frame: Measured at Study Treatment Visit 1 to establish baseline activity level (prior to onset of injury/pain)
Population: Analysis of initial Godin scores between groups
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iontophoresis With Dexamethasone | Patient Reported Outcome - Activity Level as Measured by the Godin Leisure-Time Activity Questionnaire | 71.81 score on a scale | Standard Deviation 23.61 |
| Iontophoresis With Sodium Chloride | Patient Reported Outcome - Activity Level as Measured by the Godin Leisure-Time Activity Questionnaire | 58.07 score on a scale | Standard Deviation 24.86 |
| Physical Therapy Alone | Patient Reported Outcome - Activity Level as Measured by the Godin Leisure-Time Activity Questionnaire | 65.43 score on a scale | Standard Deviation 18.54 |
p-value: 0.25ANOVA
Secondary
Patient Reported Outcome - Pain as Measured by the Wong-Baker FACES Pain Rating Scale
This scale was created for children to help them communicate their pain. The scale shows a series of faces ranging from a happy face at 0, No hurt to a crying face at 10 Hurts worst.
Time frame: Collected at final visit, which is at Visit 12, maximum of 8 weeks, or when Return to Sport Criteria are met, whichever is sooner
Population: Analysis of final FACES Pain scale ratings across all groups as available. We had 13 patients who did not provide final FACES pain data, thus that data was unable to be included in final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iontophoresis With Dexamethasone | Patient Reported Outcome - Pain as Measured by the Wong-Baker FACES Pain Rating Scale | 1.33 score on a scale of 0-10 | Standard Deviation 0.65 |
| Iontophoresis With Sodium Chloride | Patient Reported Outcome - Pain as Measured by the Wong-Baker FACES Pain Rating Scale | 1.85 score on a scale of 0-10 | Standard Deviation 1.07 |
| Physical Therapy Alone | Patient Reported Outcome - Pain as Measured by the Wong-Baker FACES Pain Rating Scale | 2.13 score on a scale of 0-10 | Standard Deviation 1.36 |
p-value: 0.29ANOVA
Secondary
Patient Reported Outcome - Percent Difficulty With Activities as Measured by the Lower Extremity Function Scale (LEFS)
The LEFS is a patient reported questionnaire that measures difficult of completing 20 activities. The maximum possible score of the LEFS is 80 points, indicating very high function. The minimum possible score is 0 points, indicating very low function. The LEFS data is reported as a percentage, calculated as XX points/80 \* 100.
Time frame: Collected at final visit, which is at Visit 12, maximum of 8 weeks, or when Return to Sport Criteria are met, whichever is sooner
Population: Analysis of final LEFS scores available across each group that completed full study participation. There were a total of 18 participants that did not complete their final LEFS scores across all three groups, so these patients have no final LEFS scores available for final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iontophoresis With Dexamethasone | Patient Reported Outcome - Percent Difficulty With Activities as Measured by the Lower Extremity Function Scale (LEFS) | 84.66 percent | Standard Deviation 17.5 |
| Iontophoresis With Sodium Chloride | Patient Reported Outcome - Percent Difficulty With Activities as Measured by the Lower Extremity Function Scale (LEFS) | 86.42 percent | Standard Deviation 12.89 |
| Physical Therapy Alone | Patient Reported Outcome - Percent Difficulty With Activities as Measured by the Lower Extremity Function Scale (LEFS) | 81.98 percent | Standard Deviation 23.38 |
p-value: 0.86ANOVA