Patellofemoral Pain Syndrome
Conditions
Keywords
Botulinum toxin type A, Patellofemoral pain syndrome, Knee Injuries, Exercise Therapy
Brief summary
The purpose of this study is to determine whether the use of botulinum toxin A injected into the lateral thigh muscle improves knee function and reduces knee pain secondary to patellofemoral syndrome. The study hypothesis is that botulinum toxin + specific exercises will be superior to specific exercises alone in improving knee function and reducing knee pain in individuals with patellofemoral syndrome.
Detailed description
Patellofemoral pain syndrome is a leading cause of knee pain in persons under 45 and is particularly common in women. The prevailing theory for the etiology of patellofemoral pain is an imbalance in force or timing of the pull of the knee extensor muscles on the patella resulting in improper tracking of the patella in the femoral grove. Specifically, the vastus medialis is thought to be ineffective in overcoming the lateral pull of the vastus lateralis. When exercises designed to focus on improving strength and timing of activation of the vastus medialis fail, surgical release of part of the attachment of the vastus lateralis to the patella is considered. Botulinum toxin temporarily blocks acetylcholine release from motor neurons and is used clinically to produce muscle relaxation. Subjects with patellofemoral syndrome will be recruited into the study. Half of the subjects will be given a placebo injection while the other half will be given an injection of Botox (Botulinum Toxin A, Allergen) into the vastus lateralis muscle. Group assignment will be randomized and a double blind protocol used. Prior to injection, the subject will record their level of knee pain, fill out several knee function questionnaires, and have the strength and endurance of their knee extensor muscles tested. All subjects will be given an exercise program designed to target strengthening of the medial thigh muscles as well as stretching of lateral structures. At 4, 6 and 12 weeks knee pain and knee function will again be assessed.
Interventions
DRUGBotulinum toxin A + exercise
Injection of 100 units Botox (Botulinum toxin type A) into the Vastus Lateralis of the study leg + 12 weeks of exercise for patellofemoral pain
DRUGPlacebo
Injection of 2 cc placebo containing 0.1cc sodium bicarbonate 8.4% (1meq/cc), 0.9cc normal saline and 1 cc of lidocaine into the vastus lateralis of the study leg followed by 12 weeks of exercise for patellofemoral pain syndrome
Sponsors
Allergan
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* retropatellar knee pain * pain with two of: prolonged sitting, climbing stairs, squatting, running, kneeling, hopping, jumping * pain with patellar palpation * symptoms minimum 1 month * Visual Analog Scale for pain (VAS) usual pain 4 of 10 on VAS \[0-10 scale, anchors 0 = no pain, 10 = worst pain imaginable\]
Exclusion criteria
* history knee surgery * history patellar dislocation * clinical evidence of meniscal lesion, ligamentous instability, traction apophysitis around the patellofemoral complex, patellar tendon pathology, chondral damage, osteoarthrosis, spinal referred pain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale Pain Ratings (VAS) | 4, 6, 12 weeks | Visual Analog Scale pain rating (VAS). 10 cm line with anchors at 0 (no pain) and 10 cm (worst imaginable pain). Scores are in cm (0 - 10) 0 no pain, higher values greater pain. Results given are for change at 12 weeks compared to baseline (week 12 score - baseline score) |
| Change in Anterior Knee Pain Scale. | 4, 6, 12 weeks | Anterior Knee Pain Scale: a 13-item questionnaire; a TOTAL score of 0 = severe disability; a score of 100 = no pain or disability. (items are scored 0-5 or 0-10). Change scores at 12 wks are reported. Inverted so positive values reflect improvement. Included items: difficulty with: weight bearing, walking, stairs, squat, run, jump, prolonged sitting; presence of limp, swelling, patellar subluxation, atrophy of thigh, reduced knee flexion. Reference: Kujala et al: Scoring of Patellofemoral Disorders. J Arthroscopic Rel Surg, 9(2)159-163, 1993 |
| Functional Index Questionnaire | 4, 6, 12 weeks | The Functional Index Questionnaire (FIQ) is a self report functional rating scale. Individuals rate eight-activities. Each activity is rated from 0 - 2 with ) being unable to perform the activity and 2 being able to perform the activity without difficulty. The total score is summed for a final score of 0 - 16. 0 indicates that the individual is ubable to perform any of the tasks, 16 indicates that the subject is able to perform all tasks without difficulty. The eight items include: walking (1 block and 1 mile), climbing stairs (2 flights and 4 flights), squatting, kneeling, prolonged sitting, and running |
| Lower Extremity Functional Scale | 4, 6, 12 weeks | The lower extremity functional scale (LEFS) is a self report questionnaire. Subjects rate 19 items related to general activities that require the lower extremities on a scale of 0 - 4. 0 = extreme difficulty or unable to perform the activity, 4 = No difficulty performing the activity. The total of all rankings are summed and divided by the maximum score (76). The score is reported as a percentage. 100% = no difficulty in performing any of the tasks. 0% = extreme difficulty or unable to perform all of the tasks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Knee Extensor Fatigue | 4, 6, 12 weeks | This is not available due to data collection errors |
| Muscle Activation During Maximal Contractions and Fatigue Contractions | 4, 6, 12 weeks | muscle activation as EMG ratios of VMO/VL at 30 degrees maximal isometric contraction at 30degrees |
| Maximal Knee Extensor Force During Concentric and Isometric Contractions | 4, 6, 12 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin A Injection + Exercise Injection of Botulinum toxin A into vastus lateralis of study limb plus exercise program | 1 |
| Placebo Injection + Exercise Placebo injection into Vastus Lateralis + exercise | 4 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Injection + Exercise | Botulinum Toxin A Injection + Exercise | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Continuous | 25.5 years STANDARD_DEVIATION 2.53 | 33 years | 27.0 years STANDARD_DEVIATION 2.47 |
| Region of Enrollment United States | 4 participants | 1 participants | 5 participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 4 |
| serious Total, serious adverse events | 0 / 1 | 0 / 4 |
Outcome results
Primary
Change in Anterior Knee Pain Scale.
Anterior Knee Pain Scale: a 13-item questionnaire; a TOTAL score of 0 = severe disability; a score of 100 = no pain or disability. (items are scored 0-5 or 0-10). Change scores at 12 wks are reported. Inverted so positive values reflect improvement. Included items: difficulty with: weight bearing, walking, stairs, squat, run, jump, prolonged sitting; presence of limp, swelling, patellar subluxation, atrophy of thigh, reduced knee flexion. Reference: Kujala et al: Scoring of Patellofemoral Disorders. J Arthroscopic Rel Surg, 9(2)159-163, 1993
Time frame: 4, 6, 12 weeks
Population: The Anterior Knee Pain Scale is a 13-item questionnaire; a score of 0 = severe disability; a score of 100 = no pain or disability. Change scores are reported. Positive values = improvement in symptoms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin A Injection + Exercise | Change in Anterior Knee Pain Scale. | 19 Units on Scale | — |
| Placebo Injection + Exercise | Change in Anterior Knee Pain Scale. | 16.7 Units on Scale | Standard Deviation 4.37 |
Primary
Functional Index Questionnaire
The Functional Index Questionnaire (FIQ) is a self report functional rating scale. Individuals rate eight-activities. Each activity is rated from 0 - 2 with ) being unable to perform the activity and 2 being able to perform the activity without difficulty. The total score is summed for a final score of 0 - 16. 0 indicates that the individual is ubable to perform any of the tasks, 16 indicates that the subject is able to perform all tasks without difficulty. The eight items include: walking (1 block and 1 mile), climbing stairs (2 flights and 4 flights), squatting, kneeling, prolonged sitting, and running
Time frame: 4, 6, 12 weeks
Population: No statistical analysis due to small number of subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A Injection + Exercise | Functional Index Questionnaire | Post 4 wk | 12 units on a scale | — |
| Botulinum Toxin A Injection + Exercise | Functional Index Questionnaire | Pre | 11 units on a scale | — |
| Botulinum Toxin A Injection + Exercise | Functional Index Questionnaire | Post 6 wk | 11 units on a scale | — |
| Botulinum Toxin A Injection + Exercise | Functional Index Questionnaire | Post 12 wk | 13 units on a scale | — |
| Placebo Injection + Exercise | Functional Index Questionnaire | Post 12 wk | 14 units on a scale | Standard Deviation 1.7 |
| Placebo Injection + Exercise | Functional Index Questionnaire | Pre | 10 units on a scale | Standard Deviation 1.7 |
| Placebo Injection + Exercise | Functional Index Questionnaire | Post 4 wk | 10 units on a scale | Standard Deviation 1.7 |
| Placebo Injection + Exercise | Functional Index Questionnaire | Post 6 wk | 10.7 units on a scale | Standard Deviation 0.6 |
Primary
Lower Extremity Functional Scale
The lower extremity functional scale (LEFS) is a self report questionnaire. Subjects rate 19 items related to general activities that require the lower extremities on a scale of 0 - 4. 0 = extreme difficulty or unable to perform the activity, 4 = No difficulty performing the activity. The total of all rankings are summed and divided by the maximum score (76). The score is reported as a percentage. 100% = no difficulty in performing any of the tasks. 0% = extreme difficulty or unable to perform all of the tasks.
Time frame: 4, 6, 12 weeks
Population: No statistical analysis due to small number of subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A Injection + Exercise | Lower Extremity Functional Scale | Pre | 69 percentage of total possible score | — |
| Botulinum Toxin A Injection + Exercise | Lower Extremity Functional Scale | Post 4 wks | 87 percentage of total possible score | — |
| Botulinum Toxin A Injection + Exercise | Lower Extremity Functional Scale | Post 6 wks | 87 percentage of total possible score | — |
| Botulinum Toxin A Injection + Exercise | Lower Extremity Functional Scale | Post 12 wks | 91 percentage of total possible score | — |
| Placebo Injection + Exercise | Lower Extremity Functional Scale | Post 12 wks | 75 percentage of total possible score | Standard Deviation 14 |
| Placebo Injection + Exercise | Lower Extremity Functional Scale | Pre | 66.7 percentage of total possible score | Standard Deviation 14.6 |
| Placebo Injection + Exercise | Lower Extremity Functional Scale | Post 6 wks | 73 percentage of total possible score | Standard Deviation 11.4 |
| Placebo Injection + Exercise | Lower Extremity Functional Scale | Post 4 wks | 71 percentage of total possible score | Standard Deviation 8 |
Primary
Visual Analog Scale Pain Ratings (VAS)
Visual Analog Scale pain rating (VAS). 10 cm line with anchors at 0 (no pain) and 10 cm (worst imaginable pain). Scores are in cm (0 - 10) 0 no pain, higher values greater pain. Results given are for change at 12 weeks compared to baseline (week 12 score - baseline score)
Time frame: 4, 6, 12 weeks
Population: analysis per protocol. Drop out not included in analysis. mean reduction in Visual Analog Scale for Pain (VAS) from start to 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin A Injection + Exercise | Visual Analog Scale Pain Ratings (VAS) | 6 cm | — |
| Placebo Injection + Exercise | Visual Analog Scale Pain Ratings (VAS) | 3.7 cm | Standard Deviation 0.33 |
Secondary
Knee Extensor Fatigue
This is not available due to data collection errors
Time frame: 4, 6, 12 weeks
Population: This is not available due to data collection errors
Secondary
Maximal Knee Extensor Force During Concentric and Isometric Contractions
Time frame: 4, 6, 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg pre | 26 Nm | — |
| Botulinum Toxin A Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg 4w | 57 Nm | — |
| Botulinum Toxin A Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg 6w | 43 Nm | — |
| Botulinum Toxin A Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg 12w | 37 Nm | — |
| Placebo Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg 12w | 42.3 Nm | Standard Deviation 5.1 |
| Placebo Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg pre | 31.3 Nm | Standard Deviation 13.1 |
| Placebo Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg 6w | 39.0 Nm | Standard Deviation 2.65 |
| Placebo Injection + Exercise | Maximal Knee Extensor Force During Concentric and Isometric Contractions | Isometric Torque 30deg 4w | 43.7 Nm | Standard Deviation 8.1 |
Secondary
Muscle Activation During Maximal Contractions and Fatigue Contractions
muscle activation as EMG ratios of VMO/VL at 30 degrees maximal isometric contraction at 30degrees
Time frame: 4, 6, 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL 6wk | 0.54 ratio VMO EMG to VL EMG | — |
| Botulinum Toxin A Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL pre | 0.91 ratio VMO EMG to VL EMG | — |
| Botulinum Toxin A Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL 12wk | 0.55 ratio VMO EMG to VL EMG | — |
| Botulinum Toxin A Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL 4wk | NA ratio VMO EMG to VL EMG | — |
| Placebo Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL 12wk | 0.69 ratio VMO EMG to VL EMG | Standard Deviation 0.33 |
| Placebo Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL pre | 0.6 ratio VMO EMG to VL EMG | Standard Deviation 0.14 |
| Placebo Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL 6wk | 0.50 ratio VMO EMG to VL EMG | Standard Deviation 0.15 |
| Placebo Injection + Exercise | Muscle Activation During Maximal Contractions and Fatigue Contractions | EMG ratio VMO/VL 4wk | 0.61 ratio VMO EMG to VL EMG | Standard Deviation 0.35 |