Background
Objectives of this trial
Secondary objectives
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To evaluate the analgesic effect of paravertebral injections of BoNT-A 3 months after its administration in chronic LBP sufferers.
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To measure the impact of paravertebral injections of 200 IU of BoNT-A in a single administration on lumbar stiffness and on spinal extensor muscle strength in patients with chronic LBP.
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To search for predictive factors of the analgesic effect of BoNT-A injections.
Materials and methods
Ethics, consent and permissions
Population
Experimental procedure
Task
Measures
Secondary judgment criteria
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Initial pain was detailed as follows: Immediate average LBP was recorded on VAS at the first injection (D0). Average pain intensity over the last week and the last month were also recorded at D0, with the same horizontal visual analogue scale.
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Lumbar pain intensity at D90 and D120 was measured on a horizontal visual analogue scale 100 mm long, with « no pain » written on one end and “maximum pain” on the other. The question asked was: “How was the intensity of your LBP over the last 8 days?” (0 = no pain; 100 = maximal pain).
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The number of days when oral pain treatment (antalgic or non-steroid anti-inflammatory, opiates were not permitted) between evaluation times was taken. Days when treatment was taken were noted as they occurred by the patient in a calendar, which was distributed at D0. We thought that a change of 25% would be significant.
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Functional disability related to LBP was measured by the Quebec Back Pain Disability Scale at each evaluation time. The higher the score (/100), the higher the disability. We considered as determined by Ostelo et al. [21] 20 points of change of the Quebec score as clinically significant.
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Quality of life was measured at each evaluation time on a horizontal visual analogue scale 100 mm long. The question asked was: "In your opinion, how was your quality of life over the last month?" (0 = no impact to 100 = major deterioration). We considered as clinically significant a change of 0.2 standard deviation (small change), 0.5 standard deviation (moderate change) and 0.8 standard deviation (large change) [22, 23].
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Inability to work was measured by a compendium of data indicating the number of sick leave days due to LBP in the 8 months preceding inclusion and during follow-up. A change of 25% was considered as clinically significant.
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Patient satisfaction regarding the effect of the treatment was measured on a horizontal visual analogue scale 100 mm long at each evaluation time. The question asked at each evaluation was: "In your opinion, how is the overall efficacy of the treatment that you have received?"(0 = no efficacy; 100 = high efficacy). A change superior than 50% was considered as clinically significant.
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Spinal mobility was measured at each evaluation time by using Schober & Macrae’s test (Miller 1984). Two lines were drawn 10 cm above the postero superior iliac spine and 5 cm below the postero superior iliac spine. The distances in a standing position and in anteflexion were measured. A difference less than 4 cm was considered as a spine stiffness.
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Spinal muscle strength was measured by flexion and extension isokinetic technique at a speed of 60° per second before the injections, at D30, D120, D150 and D240. A variation of strength up to 20% or a reversal of the flexor/extensor ratio was considered as clinically significant.
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MODIC classification of discopathy and Hadar classification of the rector spinae muscles were based on MRI performed in the previous year. The MODIC measures are divided in 3 classes: [24]: there were type 1 (inflammatory phase), type 2 (fatty phase) and type 3 (marked sclerosis adjacent to the endplates). We collected the data in order to look for predictive factors for efficacy of BoNT-A.
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Tolerance to BoNT-A injections was studied by actively asking at each visit for possible side effects (pain at injection points, sensation of general weakness, falling, nausea, diplopia, dry mouth).
Statistical analysis
Results
Flow diagram (Figure 1)
Description of the population at baseline (standard deviations are noted in parentheses) (Table 1)
Patients | Botulinum toxin | Placebo | t-test (p) |
---|---|---|---|
Sample size |
N = 9 |
N = 10 | |
Men/Women | 3/6 | 0/10 | 0.047 |
Age: mean (SD) in years | 38.1 (5.94) | 38.2 (10.27) | 0.49 |
Spinal pain intensity: mean (SD) /100 mm | 59.33 (15.71) | 58.70 (15.89) | 0.47 |
Radicular pain intensity: mean (SD) /100 mm | 42.89 (26.98) | 28.40 (27.16) | 0.13 |
Pain intensity during last month: mean (SD) /100 mm | 63.11 (25.70) | 66.70 (24.50) | 0.38 |
Pain intensity during last week: mean (SD) /100 mm | 67.67 (22.37) | 57.50 (25.63) | 0.18 |
Quebec initial score mean (SD) /100 mm | 52.56 (11.64) | 51.70 (16.55) | 0.45 |
Disability during last 8 months: mean (SD) /100 mm | 58.22 (82.29) | 151.6 (96.56) | 0.018 |
Disability during last month: mean (SD) /100 mm | 7.44 (12.99) | 13.4 (14.55) | 0.18 |
Quality of life at inclusion: mean (SD) /100 mm | 76.56 (16.41) | 65.00 (17.80) | 0.08 |
Number of days with painkillers or anti-inflammatories: number (SD) | 19.67 (13.44) | 14.1 (12.57) | 0.18 |
Paravertebral painful point pressure Right/Left/Bilateral | 4/3/2 | 4/0/6 | |
Stiffness: number | 8 | 6 | 0.08 |
Tendency to cough: number | 5 | 7 | 0.27 |
Instability: number | 9 | 8 | 0.08 |
Schober’s test: centimeter (SD) | 4.22 (1.30) | 3.95 (1.77) | 0.35 |
Hand-ground distance: centimeter (SD) | 28.60 (13.60) | 20.60 (15.60) | 0.13 |
Spinal pain: mean (SD) | 3.13 (1.46) | 3.60 (1.84) | 0.27 |
Paravertebral pain: number | 2 | 5 | 0.33 |
Lasegue sign: number | 0 | 0 | |
Pseudo-Lasegue sign: mean (SD) | 0.25 (0.46) | 0.5 (0.53) | 0.15 |
Disco-radicular conflict: number | 0 | 1 | 0.17 |
MODIC L1-L2 0/1/2/3 | 9/0/0/0 | 9/0/1/0 | 0.17 |
MODIC L2-L3 0/1/2/3 | 9/0/0/0 | 9/0/1/0 | 0.17 |
MODIC L3-L4 0/1/2/3 | 9/0/0/0 | 9/0/1/0 | 0.17 |
MODIC L4-L5 0/1/2/3 | 9/0/0/0 | 9/0/0/1 | 0.17 |
MODIC L5-S1 0/1/2/3 | 5/3/1/0 | 4/3/2/1 | 0.15 |
HADAR L1-L2 0/1/2/3 | 8/1/0/0 | 8/2/0/0 | 0.31 |
HADAR L2-L3 0/1/2/3 | 6/3/0/0 | 7/3/0/0 | 0.44 |
HADAR L3-L4 0/1/2/3 | 4/5/0/0 | 7/1/2/0 | 0.33 |
HADAR L4-L5 0/1/2/3 | 1/6/2/0 | 3/4/3/0 | 0.37 |
HADAR L5-S1 0/1/2/3 | 1/4/4/0 | 0/4/6/0 | 0.18 |
Isokinetic maximum strength: n/m (SD) | 115.33 (58.63) | 114.44 (37.63) | 0.49 |
Isokinetic endurance: n/m (SD) | 89.11 (62.50) | 77.33 (53.86) | 0.34 |
Flexors/extensors ratio at 60°: % (SD) | 123.63 (37.56) | 119.36 (49.51) | 0.42 |
Between-group comparisons (Table 2)
Level of LBP intensity
Number of patients (n) A/B | Mean group A | Standard deviation group A | Mean group B | Standard deviation group B |
p-value | ||
---|---|---|---|---|---|---|---|
Average lumbar pain over last 8 days by visual analogue scale (/100 mm) |
D0
| 18/19 | 67.70 | 24.64 | 60.35 | 28.07 |
p = 0.43 |
D30
| 18/19 | 63.12 | 18.92 | 63.12 | 18.92 |
p = 0.75 | |
D90
| 15/16 | 62.60 | 27.39 | 58.43 | 24.66 |
p = 0.80 | |
D120
| 15/16 | 60.87 | 26.83 | 55.87 | 32.50 |
p = 0.70 | |
Average root pain over last month by visual analogue scale (/100 mm) |
D30
| 18/19 | 60.29 | 22.99 | 53.47 | 33.88 |
p = 0.45 |
D90
| 15/16 | 42.07 | 37.40 | 27.57 | 33.05 |
p = 0.52 | |
D120
| 15/16 | 56.73 | 25.33 | 46.20 | 30.42 |
p = 0.70 | |
Number of days with significant or very significant pain |
D30
| 18/19 | 13.29 | 9.88 | 15.18 | 12.82 |
p = 0.55 |
D90
| 15/16 | 11.43 | 10.45 | 11.71 | 16.94 |
p = 0.44 | |
Functional disability related to low-back pain by Quebec Back Pain Disability Scale (/100) |
D0
| 18/19 | 51.53 | 16.19 | 52.35 | 20.16 |
p = 0.89 |
D30
| 18/19 | 53.76 | 13.18 | 52.29 | 20.74 |
p = 0.77 | |
D90
| 15/16 | 53.07 | 17.75 | 45.93 | 22.82 |
p = 0.47 | |
D120
| 16/16 | 52.87 | 21.69 | 42.93 | 23.70 |
p = 0.48 | |
Inability to work during last 30 days (/30) |
D0
| 18/19 | 11.00 | 14.56 | 11.06 | 14.55 |
p = 0.99 |
D30
| 18/18 | 12.41 | 15.17 | 9.56 | 14.25 |
p = 0.35 | |
D90
| 15/16 | 12.41 | 14.59 | 9.69 | 17.93 |
p = 0.46 | |
D120
| 15/16 | 8.00 | 13.73 | 12.00 | 15.21 |
p = 0.34 | |
Estimated impact of low-back pain on quality of life (/100) |
D0
| 18/19 | 71.41 | 21.70 | 64.47 | 24.61 |
p = 0.37 |
D30
| 18/19 | 68.71 | 18.85 | 64.06 | 23.33 |
p = 0.44 | |
D90
| 15/16 | 63.47 | 23.72 | 58.57 | 23.33 |
p = 0.38 | |
D120
| 15/16 | 61.00 | 30.01 | 60.67 | 29.63 |
p = 0.96 | |
Number of days when pain medication or anti-inflammatories were necessary in last 30 days (/30) |
D0
| 18/19 | 17.06 | 13.65 | 15.35 | 14.69 |
p = 0.71 |
D30
| 18/19 | 16.06 | 13.21 | 13.41 | 13.44 |
p = 0.51 | |
D90
| 15/16 | 15.73 | 13.85 | 11.50 | 13.82 |
p = 0.79 | |
D120
| 15/16 | 14.80 | 14.87 | 13.53 | 14.54 |
p = 0.86 | |
Patients’ assessment of efficacy of treatment (/100) |
D30
| 18/19 | 0.76 | 1.15 | 0.94 | 1.14 |
p = 0.62 |
D90
| 15/16 | 1.33 | 1.80 | 1.43 | 1.60 |
p = 1.00 | |
D120
| 15/16 | 1.47 | 1.77 | 1.73 | 1.62 |
p = 1.00 | |
Spinal flexibility measured by Schoeber Macrae’s test (cm) |
D0
| 18/19 | 5.00 | 2.34 | 4.21 | 1.86 |
p = 0.22 |
D30
| 18/19 | 4.76 | 1.88 | 4.32 | 1.67 |
p = 0.48 | |
D90
| 15/16 | 4.00 | 1.18 | 4.54 | 1.31 |
p = 0.23 | |
D120
| 15/16 | 4.23 | 1.55 | 5.53 | 2.28 |
p = 0.18 | |
Hand-ground distance (cm) |
D0
| 18/19 | 26.17 | 13.32 | 25.64 | 14.03 |
p = 0.93 |
D30
| 18/19 | 26.35 | 14.02 | 26.85 | 12.89 |
p = 0.92 | |
D90
| 15/16 | 24.87 | 14.51 | 16.79 | 10.17 |
p = 0.35 | |
D120
| 15/16 | 27.53 | 12.18 | 21.93 | 13.08 |
p = 0.25 | |
Isokinetic maximum strength (n/m) |
D0
| 16/17 | 116.00 | 45.53 | 126.40 | 63.41 |
p = 0.78 |
D30
| 15/18 | 120.93 | 53.30 | 134.40 | 63.67 |
p = 0.70 | |
D120
| 13/14 | 126.69 | 67.20 | 135.07 | 50.35 |
p = 0.70 | |
Isokinetic endurance (n/m) |
D0
| 16/17 | 100.27 | 51.63 | 102.33 | 63.24 |
p = 0.81 |
D30
| 15/17 | 96.07 | 53.38 | 108.73 | 69.00 |
p = 0.76 | |
D120
| 15/14 | 103.17 | 63.74 | 111.79 | 57.67 |
p = 0.65 | |
Isokinetic maximum force ratio flexors/extensors (%) |
D0
| 16/17 | 115.85 | 31.13 | 119.72 | 38.95 |
p = 0.36 |
D30
| 15/17 | 122.93 | 33.83 | 107.86 | 24.41 |
p = 0.16 | |
D120
| 13/14 | 111.54 | 24.29 | 102.88 | 23.53 |
p = 0.72 |
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Root pain intensity over the last month:
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Number of days with significant or very significant pain: