ABSTRACT
There is some evidence of retroviral infection in ALS. A randomized, double-blind, placebo-controlled trial of indinavir in ALS was performed to assess safety and efficacy trends. Nephrolithiasis and gastrointestinal side effects were frequent with indinavir treatment. Group differences in the rate of decline were not significant between the groups for the ALS Functional Rating Scale (p = 0.36) or for the secondary variables. The toxicity and negative efficacy trends discourage further indinavir trials in ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/drug therapy , Central Nervous System/drug effects , Indinavir/administration & dosage , Indinavir/adverse effects , Amyotrophic Lateral Sclerosis/physiopathology , Amyotrophic Lateral Sclerosis/virology , Central Nervous System/physiopathology , Central Nervous System/virology , Double-Blind Method , Female , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/adverse effects , Humans , Kidney Calculi/chemically induced , Male , Middle Aged , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/adverse effects , Pilot Projects , Placebos , Riluzole/administration & dosage , Riluzole/adverse effects , Treatment FailureABSTRACT
OBJECTIVE: To determine whether the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRSr), a predictor of survival time in ALS clinical trials, predicts survival time in an ALS clinic population. METHODS: The authors prospectively evaluated 267 consecutive patients with ALS at first visit to an ALS clinic using the ALSFRSr and pulmonary function testing. The association of ALSFRSr score at baseline with death or tracheostomy in ALS was examined using Cox proportional hazards models, adjusting for age at baseline, sex, and symptom duration. RESULTS: Of 267 patients with ALS, 103 (39%) reached the endpoint, defined as either death (79 patients) or tracheostomy (24 patients), during a mean follow-up of 1.0 +/- 0.7 years. Among the 103 patients who reached the endpoint during follow-up, 77 (75%) had a baseline ALSFRSr score of less than 38 (the median baseline score of all patients), compared to 53 of 164 (32%) who remained alive without tracheostomy. Patients with a total ALSFRSr score below the median had a 4.4-fold increased risk of death or tracheostomy compared to those who scored above the median (HR: 4.38, 95% CI: 2.79 to 6.86, p < 0.001). Both the total ALSFRSr score at baseline (HR: 0.94, 95% CI: 0.91 to 0.98, p < 0.001) and forced vital capacity at baseline (HR: 0.99, 95% CI: 0.98 to 1.00, p = 0.02) were associated with death or tracheostomy when included in the same Cox model. CONCLUSIONS: In an ALS clinic population, the total Amyotrophic Lateral Sclerosis Functional Rating Scale-revised score at baseline is a strong predictor of death or tracheostomy independently of forced vital capacity and after adjustment for age at baseline, sex, and symptom duration.
