Dataset Information

Phase IIB Randomized Trial on the Use of 4-Aminopyridine in Guillain-Barre Syndrome.

ABSTRACT:

Objective

To determine the safety and efficacy of orally delivered 4-aminopyridine (4-AP) in persons with Guillain-Barré Syndrome (GBS) >6 months from initial diagnosis.

Design

A randomized, double-blind, placebo-controlled, crossover study.

Setting

Tertiary care clinical outpatient program.

Participants

Nineteen participants enrolled (14 male, 5 female; N=19), neurologic impairment secondary to GBS and functional loss on the FIM motor score (stable for ≥12mo) and >3.0 but <5.0 on the American Spinal Injury motor scale. Twelve participants (mean age, 59y; range, 23-77y) completed the study.

Interventions

A 4-AP dose-escalation study with 8 weeks in each period with a 3-week washout period, followed by 3 months open-label follow-up.

Main outcome measures

FIM motor score was the primary outcome measure; also evaluated were the American Spinal Injury motor strength score (all limbs), handheld dynamometer, 6-minute walk test, Medical Outcomes Study 12-Item Short Form, Center for Epidemiological Studies Depression scale, Positive and Negative Affect Schedule, pain, GBS disability scale, Jepsen-Taylor Hand Function Test, Minnesota Manual Dexterity Test and Minnesota Rate of Manipulation Test, Get Up and Go Test, McGill Pain Inventory, Craig Handicap Assessment and Reporting Technique, and participant self-evaluation.

Results

Seven participants discontinued the study prematurely: 3 because of adverse events, 3 because of travel difficulties or relocation, and 1 because of pretreatment laboratory abnormalities. After removing 3 participants with maximum FIM scores, 4-AP arm trended superior to placebo (P=.065). Patients subjectively could always tell when they were on the active agent usually by tingling sensations or a sense of wellness. No statistically significant differences were found for other outcome measures although there were strong trends.

Conclusions

This study demonstrates the safety of 4-AP in the patient population with GBS as the predominate goal of the study. A trend toward improved function after treatment was noted with most patients electing to stay on the medication after the trial.

SUBMITTER: Meythaler JM

PROVIDER: S-EPMC8212006 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundGuillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome.MethodsAutoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed.ResultsNone of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors.ConclusionOur study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS.

Project description:INTRODUCTION:About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia. METHODS:This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first). FINDINGS:Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P?=?1). There was no significant difference between groups for the time to onset of pneumonia (P?=?0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P?<?000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P?=?0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events. CONCLUSIONS:In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation. TRIAL REGISTRATION:ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1.