Subjects

The study was held at the rheumatology clinic of the Département de l’appareil locomoteur (DAL), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Patients selection was as follows: inclusion criteria: 1) aged from 20 to 65 year old, male or female, suffering from non specific low back pain with or without symptoms in the lower extremity for a period between 12 and 26 weeks; 2) the usual medication can be continued; exclusion criteria: 1) spinal fracture or surgery within the previous 6 months; 2) pregnancy; 3) neoplasia; 4) spinal infection; 5) spinal inflammatory arthritis; 6) low back pain of visceral origin; 7) severe sensitive and/or motor radicular deficit from nerve root origin of less than 6 months; 8) score of 3/5 or more on the Waddell Score[36]; 9) on sick leaves from work for 6 months or more; 10) psychiatric disorders; 11) opioid medication; 12) patient unable to collaborate (linguistic barrier; cognitive impairments); 13) radiologic abnormalities other than degenerative disease and; 14) clinical neurogenic claudication.

Before the study, we calculated the sample size needed to detect a predicted effect of an ODI score difference of 5.5 with a SD of 10[22, 37]. We predicted that 52 patients per group were needed to reach a power of 0.8 with a type I error probability of 5%. During the experimental phase, we had problems with patient recruitment and were forced, for financial reasons, to stop the recruitment process before the target sample size was reached. This decision was taken without knowledge of study findings.

All eligible patients were given written information about the study and were asked to provide written consent before participating. Afterwards, they were asked to attend an initial evaluation visit in order to perform clinical tests and fill in self-questionnaires, supervised by a physiotherapist not involved in the patients’ therapies and blinded to the treatment groups. The same physiotherapist supervised subsequent patients’ evaluation visit after the 8th therapeutic session, and at 3 and 6 months after the end of the treatment. The study protocol was approved by the Ethics Committee of Clinical Research, Faculty of Biology and Medicine, University of Lausanne, Switzerland.

Randomization

Following the initial evaluation visit, patients were randomly assigned to their treatment group. Concealment allocation was performed by using a randomized table of numbers[38], from which every four consecutive numbers were retained. Individual index cards with the corresponding number were folded and placed in consecutively numbered, sealed opaque envelopes. Even numbers were allocated to the manual therapy (MT) group and odd numbers to the sham therapy (ST) group.

Treatments

Treatments consisted of a physiotherapy evaluation and 8 therapeutic sessions (1–2 sessions per week) over a period of 4 to 8 weeks.

The physiotherapy evaluation (45 minutes) included: 1) a standard physiotherapy assessment for non specific low back pain[39]; 2) an educational information on the low back anatomy and biomechanics, ways to protect the spine during activities of daily living and rest during episodes of pain (presented in a 6-page booklet); 3) 2 home mobility exercises (pelvic tilt and low back lateral flexion, in supine), to be performed daily, twice a day, 2 sets of 10 repetitions. After the 3rd or 4th therapeutic session, the recommendation of home exercises changes to stretching and motor control exercises (see active exercises for dosage and progression). Home exercises were reviewed at the beginning of each therapeutic session and recorded daily by patients in a diary.

The therapeutic sessions (30 minutes) consisted of: for the MT group, 5 to 10 minutes of MT intervention followed by active exercises (AE); for the ST group, 5 to 10 minutes of ST intervention followed by AE.

I. MT/ST intervention

The MT intervention, performed by a single physiotherapist of 15 years of experience, comprises the use of one (or more) of the following techniques:

Passive accessory intervertebral movements, a central or unilateral postero-anterior pressure applied on painful or stiffed vertebral segment(s) with the patient lying prone[39].

Muscle-energy techniques, a hold-relaxed technique performed on an ilium dysfunction with the patient side lying[25].

High velocity, low amplitude dynamic thrust (manipulation), a rotational-lateral flexion thrust performed on a stiffed vertebral segment(s) with the patient side lying[23, 40].

The ST intervention, delivered by 2 physiotherapists of 5 and 25 years of working experience at the rheumatology unit of the DAL (CHUV), relied on detuned ultrasound on the patient’s painful and/or inflammatory site. The patient did not know the ultrasound was inactivated and, therefore, ineffective. The choice of the therapist depended exclusively on immediate availability, work schedule and vacation.

II. Active exercises (AE)

Before the start of the clinical phase, the 3 treating therapists agreed on a protocol of therapeutic exercises (type; dosage; progression).

Mobility exercises throughout the 8 therapeutic sessions to improve patient’s spinal range of motion and pain. For the first 2 sessions, pelvic tilt and low back lateral flexion exercises were performed in the supine position, 3 sets of 5 to 10 repetitions. From session 3, the same exercises were adapted in sitting on a stable plane, then on a swiss ball.

Passive stretching exercises after the 2nd session, for muscle groups that tend to shorten (erector spinae, hamstring, iliopsoas, rectus femoris, piriformis), to relieve muscular tension and improve low back mobility. They were performed 3 times for 20 seconds.

Motor control exercises at the 4th session for active recruitment of stabilizing trunk muscles[41]. Patients were asked to contract their transverse abdominus and/or multifidus muscle at 20% of maximum voluntary contraction, under visual and tactile supervision, for 10 to 30 seconds, 5 to 10 times. At first, the exercises were performed supine, then seated and, finally, in the standing position. Progression went from static to dynamic contraction.

Strengthening exercises at the 6th or 7th session to increase strength of weak superficial trunk muscles. They were performed at 60–70% of maximum voluntary contraction, against the resistance of an adapted rubber band, 2 sets of 20 repetitions.

The same physiotherapist who performed the preceding MT/ST intervention supervised the active exercises.

At the end of the 8 therapeutic sessions, no particular recommendations were given to patients but to continue their exercises if desired. This issue was not investigated at the 3- and 6-month evaluation visits.

Outcome measures

Immediate analgesic effect, evaluating the MT/ST intervention’s efficiency, was obtained by measuring pain intensity (Visual Analogue Scale – VAS-pain, immediate effect) before and immediately after the manual therapy or detuned ultrasound intervention at each therapeutic session. To evaluate the treatment efficiency, pain intensity (VAS-pain, average 48-hour pain), disability (Oswestry Disability Index - ODI), fear-avoidance beliefs (Fear-Avoidance Beliefs Questionnaire - FABQ) and Sorensen and Shirado tests were determined before treatment, after the 8th therapeutic session, and at 3- and 6-month after the end of treatment.

Primary outcomes

1)VAS-pain is a self-report of clinical pain intensity, consisting of a 10 cm horizontal line scale on which is added the statements “no pain” on the left and “maximum intensity of pain” on the right [42]. Firstly, to evaluate VAS-pain (immediate effect), patients were asked to rate their current pain twice at each therapeutic session. Secondly, to evaluate VAS-pain (average 48-hour pain), patients were asked to rate their average pain during the last 48 hours before each evaluation visit. VAS-pain ratings are reported to have good reliability and concurrent validity when compared to other methods of pain measurement [43]. 2) ODI is a self-rating questionnaire used to evaluate functional physical disability [44]. It includes 10 sections of 6 propositions, each of them rated on a 0–5 scale; the maximum possible score is 50. Relative values are reported (total score/total possible score × 100%). Higher is the score, worst is the disability. For CLBP, it has good level of internal consistency and test-retest reliability [45].

Secondary outcomes

1)FABQ measures level of fear and avoidance beliefs about work and physical activity in patients with low back pain [46]. The instrument consists of two subscales, a four-item physical activity subscale (FABQ-pa), and a seven-item work subscale (FABQ-wk). Each item is scored from 0 to 6 and summed to produce the subscale score. Possible scores range from 0–28 and 0–42 for the FABQ-pa and FABQ-wk, respectively. This questionnaire has good level of internal consistency and test-retest reliability [42, 47]. 2) Sorensen test evaluates the erector spinae muscles endurance [48]. 3) Shirado test assesses the abdominal muscles endurance [49]. Sorensen and Shirado tests are relatively safe, easy to perform and have high reliability in subjects with and without non specific low back pain.

Statistical analysis

The effect of intervention (MT vs. ST), time and the intervention-time interaction on the immediate effect of the intervention (VAS-pain, immediate effect) at each time point (pain after minus pain before) was analysed by means of random coefficient linear mixed models. In these models, the effects of the independent variables are allowed to vary between subjects. In other words, subjects were allowed to have their individual slope for the outcome over time. To control for potential bias due to regression to the mean, pain measured before each therapeutic session was entered in the model as time-varying covariate.

The effect of treatment (MT + AE vs. ST + AE), time and the treatment-time interaction on the six outcome variables pain intensity (VAS-pain, average 48-hour pain), ODI, FABQ-wk, FABQ-pa, Sorensen and Shirado, evaluated after the 8th therapeutic session, and at 3 and 6 months after the end of treatment, were estimated by means of random coefficient linear mixed models. The outcomes’ baseline values (measures before treatment) were entered as a covariate to adjust for baseline differences between treatments. First, the analysis was performed with the interaction. When the effect was not significant, the analysis was repeated without the interaction.

Because two primary outcomes were assessed (i.e., functional physical disability and pain), we considered an alpha level of 0.025 for those two outcomes. The conventional alpha = 0.05 was kept for inference about the secondary outcomes.