Pinto 2012.
| Methods | A double‐blind (assessors and participants) RCT which took place in Portugal | |
| Participants | 26 participants with definite (4 participants) or probable (22 participants) ALS, as defined by the revised El Escorial criteria, recruited immediately after diagnosis Disease onset: bulbar 4 participants, spinal in 22 participants (10 in upper limbs and 12 in lower limbs) Inclusion criteria Age at disease onset between 18 and 75 years; disease duration < 24 months at entry; ALSFRS > 24/40 at entry; and informed consent Exclusion criteria Familial ALS, pregnant women and people with additional problems (e.g. diabetes, lung disorders, frontal dementia, perioral weakness preventing adequate lip sealing, and upper limb weakness sufficient to prevent respiratory training), people with FVC < 70% or MIP and MEP < 50% of the predicted value, and ulnar lesion or absent ulnar nerve motor response 1 person in each group dropped out less than 2 months after study entry: 1 with rapidly progressive spasticity (active treatment group); the other (sham IMT group) was lost to follow‐up. 24 participants finished the first 4 months of the study and were included in the statistical analysis Group 1 (active IMT) N = 13 M/F = 7/6 Age (mean ± SD) = 57.14 ± 9.3 yrs ALSFRS (mean ± SD) = 34.39 ± 3.64 Group 2 (sham IMT) N = 13 M/F = 11/2 Age (mean ± SD) = 56.8 ± 8.7 yrs ALSFRS (mean ± SD) = 33.5 ± 3.8 There was no significant difference between the two groups at entry |
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| Interventions | Active or sham IMT twice daily for a 10‐min period Training group (group 1) Active IMT protocol for 8 months Control group (group 2) Sham training for the first 4 months, followed by an identical active IMT protocol for 4 months In the active exercise period, both in group 1 and group 2, the threshold load was set to 30% to 40% of the MIP. The sham‐period exercise (first 4 months for participants in group 2) consisted of breathing through the respiratory device with the lowest possible load, i.e. 9 cmH₂O |
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| Outcomes | Participants were evaluated 3 times: at entry (T0), end of the 1st 4‐month period (T1), and at the end (T2) of the study (8 months) Primary outcome: ALSFRS Secondary outcomes: respiratory function tests (sitting and supine FVC, MIP and MEP, PEF, MVV, SNIP), P0.1, nocturnal pulse oximetry, diaphragmatic motor responses by percutaneous bipolar phrenic stimulation, Neurophysiological Index, dyspnoea by a visual analogue scale, Fatigue Severity Scale, Borg scale, Hamilton Rating Scale for Depression, Epworth Daytime Sleepiness Scale, Functional Independent Measure, quality of life (EuroQol‐5D) and participants were assessed clinically and asked to say whether they felt better, worse or unchanged |
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| Funding | The 1st author (SP) had a grant from the “Fundação para a Ciência e a Tecnologia”, SFRH/BD/30714/2006 This work was supported by “Fundação para a Ciência e Tecnologia” ‐PIC/IC/82765/2007 | |
| Conflicts of interest | The authors had no conflicts of interest | |
| Notes | Trial author contacted for further details | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote (from report): "all subjects were independently randomized, in blocks of six, into two treatment groups" |
| Allocation concealment (selection bias) | Low risk | The randomization was done by an external independent randomizer. At the time of each inclusion, the envelope with the number of inclusion was opened and the allocated group study was known by one of the authors, SP, who trained the participants (details from correspondence with authors) |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote (from report): "They were all informed that the trial was devised to determine the best respiratory training protocol. Those included in group 2 were not aware of the placebo training during the first half of this study, as
the device was set for them at the minimum load value" Quote (from correspondence): "the patients were scientifically blinded to which group was 'the best'" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote (from correspondence): the person "who performed the functional evaluation and the phrenic nerve studies, was blinded to the allocated study group" Quote (from trial report): "The ALSFRS was applied by a blinded evaluator (MdeC) to derive the total score" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote (from report): "One patient in each group dropped out less than two months after study entry: one (group 1) had rapidly progressive spasticity; the other (group 2) was lost to follow‐up" |
| Selective reporting (reporting bias) | Low risk | Data reported for all outcomes |
| Other bias | Low risk | The trial appears to be free of other sources of bias |