Muscle Injury, Total Hip Arthroplasty
Conditions
Keywords
THA, Muscle injury
Brief summary
Local administration of PLX-PAD single dose, intra-muscular injection for the regeneration of injured gluteal musculature after Total Hip Arthroplasty (THA).
Detailed description
One of the main problems when performing THA via the standard transgluteal approach is the necessary injury of the gluteus medius muscle. The consecutive decrease of contractile muscle substance and the substitution by scar tissue leads to functional deficits of the pelvic-stabilizing musculature with an insufficiency limp in a large number of patients. In the long run the lack of musculature leads to a decrease in bone substance at the insertion sites of the gluteal muscles of the proximal femur. The present study has the aim of establishing a new therapy for iatrogenic gluteal muscle damage. The hypothesis of the present proposal is that intra-muscular (IM) injection of PLX-PAD into the iatrogenically injured gluteus medius muscle after THA results in an improved regeneration of the skeletal muscle tissue and consecutively in an improved functional outcome. Subjects will be assigned to receive one of the two targeted doses of PLX-PAD or placebo. On the treatment day, after suturing the gluteus medius muscle PLX-PAD or placebo will be applied directly to the site of laceration. Patients will be followed up for efficacy assessment up to week 26 and for safety assessment (Adverse events, vital signs, ECG, routinf lab and immunological testing) up to week 52 after THA. Patients will be phoned at week 104 in order to inquire about the occurence of new cancer.
Interventions
BIOLOGICAL150M PLX-PAD
Single course, multiple IM injections
BIOLOGICAL300M PLX-PAD
Single course, multiple IM injections
BIOLOGICALPlacebo
Single course, multiple IM injections
Sponsors
Pluristem Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects between 50 to 75 years of age 2. Scheduled THA 3. ASA Score ≤ 3 4. Signed written informed consent
Exclusion criteria
1. Muscle diseases 2. Severe neurological diseases 3. Opioid long term medication 4. Pain chronification \> stadium II of Gerbershagen 5. Immunosuppression due to illness or medication 6. Ankylosing spondylitis 7. History of ectopic bone formation of any localisation 8.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength. | Day 0 to Week 26 | Change from Visit 2 (Day 0) to Week 26 in the maximal voluntary isometric contraction (MVIC) moment of the injured side as measured by isometric dynamometry to assess Gluteus Medius force strength. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Day 0 to Week 26 in Muscle Volume. | Day 0 to Week 26 | Change from Visit 2 (Day 0) to Week 26 in Muscle Volume as Measured by MRI. |
| Change From Day 1 to Week 12 in Mean Fiber Diameter. | Day 1 to Week 12 | Change from Visit 3 (Day 1) to Week 12 in Mean Fiber Diameter as Measured by Muscle Biopsy. |
| Change From Day 0 to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift . | Day 0 to Week 26 | Change from Visit 2 (Day 0) to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift as Measured by Gait Analysis |
| Change From Day 0 to Week 26 in the Visual Analog Scale (VAS) Pain Score. | Day 0 to Week 26 | Visual Analog Scale (VAS) Pain Score ranges from 0 mm (no pain) to 100 mm (worse possible pain) |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PLX-PAD Low Dose PLX-PAD low dose: Single treatment, multiple injections | 7 |
| PLX-PAD High Dose PLX-PAD high dose: Single treatment, multiple injections | 6 |
| Placebo Placebo: Single treatment, multiple injections | 7 |
| Total | 20 |
Baseline characteristics
| Characteristic | PLX-PAD High Dose | Placebo | PLX-PAD Low Dose | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 7.4 | 64.3 years STANDARD_DEVIATION 6.4 | 65.4 years STANDARD_DEVIATION 5.9 | 64.8 years STANDARD_DEVIATION 6.2 |
| Region of Enrollment Germany | 6 participants | 7 participants | 7 participants | 20 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 1 / 7 | 0 / 6 | 1 / 7 |
Outcome results
Primary
Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength.
Change from Visit 2 (Day 0) to Week 26 in the maximal voluntary isometric contraction (MVIC) moment of the injured side as measured by isometric dynamometry to assess Gluteus Medius force strength.
Time frame: Day 0 to Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PLX-PAD Low Dose | Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength. | 31.17 Newtons | Standard Error 6.97 |
| PLX-PAD High Dose | Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength. | 20.36 Newtons | Standard Error 7.61 |
| Placebo | Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength. | 5.43 Newtons | Standard Error 6.46 |
p-value: 0.006795% CI: [7.61, 43.86]Mixed Models Analysis
p-value: 0.1895% CI: [-7.12, 36.99]Mixed Models Analysis
Secondary
Change From Day 0 to Week 26 in Muscle Volume.
Change from Visit 2 (Day 0) to Week 26 in Muscle Volume as Measured by MRI.
Time frame: Day 0 to Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PLX-PAD Low Dose | Change From Day 0 to Week 26 in Muscle Volume. | 24.42 mm3 | Standard Error 4.18 |
| PLX-PAD High Dose | Change From Day 0 to Week 26 in Muscle Volume. | 15.62 mm3 | Standard Error 4.91 |
| Placebo | Change From Day 0 to Week 26 in Muscle Volume. | 6.39 mm3 | Standard Error 4.35 |
p-value: 0.00495% CI: [6.03, 30.02]Mixed Models Analysis
p-value: 0.1995% CI: [-4.72, 23.17]Mixed Models Analysis
Secondary
Change From Day 0 to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift .
Change from Visit 2 (Day 0) to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift as Measured by Gait Analysis
Time frame: Day 0 to Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PLX-PAD Low Dose | Change From Day 0 to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift . | 0.43 Ratio | Standard Error 0.13 |
| PLX-PAD High Dose | Change From Day 0 to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift . | 0.28 Ratio | Standard Error 0.14 |
| Placebo | Change From Day 0 to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift . | 0.27 Ratio | Standard Error 0.13 |
p-value: 0.495% CI: [-0.21, 0.53]Mixed Models Analysis
p-value: 0.96Mixed Models Analysis
Secondary
Change From Day 0 to Week 26 in the Visual Analog Scale (VAS) Pain Score.
Visual Analog Scale (VAS) Pain Score ranges from 0 mm (no pain) to 100 mm (worse possible pain)
Time frame: Day 0 to Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PLX-PAD Low Dose | Change From Day 0 to Week 26 in the Visual Analog Scale (VAS) Pain Score. | -31.76 mm | Standard Error 5.9 |
| PLX-PAD High Dose | Change From Day 0 to Week 26 in the Visual Analog Scale (VAS) Pain Score. | -37.87 mm | Standard Error 6.53 |
| Placebo | Change From Day 0 to Week 26 in the Visual Analog Scale (VAS) Pain Score. | -48.57 mm | Standard Error 5.97 |
p-value: 0.0595% CI: [0.16, 33.47]Mixed Models Analysis
p-value: 0.2495% CI: [-7.26, 28.65]Mixed Models Analysis
Secondary
Change From Day 1 to Week 12 in Mean Fiber Diameter.
Change from Visit 3 (Day 1) to Week 12 in Mean Fiber Diameter as Measured by Muscle Biopsy.
Time frame: Day 1 to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PLX-PAD Low Dose | Change From Day 1 to Week 12 in Mean Fiber Diameter. | 1.25 microns | Standard Error 3.27 |
| PLX-PAD High Dose | Change From Day 1 to Week 12 in Mean Fiber Diameter. | 0.28 microns | Standard Error 3.23 |
| Placebo | Change From Day 1 to Week 12 in Mean Fiber Diameter. | -5.21 microns | Standard Error 3.24 |
p-value: 0.1995% CI: [-3.5, 16.41]ANCOVA
p-value: 0.2595% CI: [-4.29, 15.26]ANCOVA