Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)

Primary objective:

Efficacy of pioglitazone (45 mg/day) as add-on therapy to standard therapy with riluzole in patients with ALS compared to placebo in terms of survival (mortality defined exclusively as death).

This is a prospective, multicentre, randomised, stratified, parallel-group, double-blind trial comparing placebo with 45 mg pioglitazone as add-on therapy to 100 mg riluzole in ALS in 220 enrolled patients. For entry, the El Escorial Criteria for diagnosis will be used. The duration of treatment will be 18 months. The primary endpoint will be subjected to a confirmatory analyses. Secondary variables will be incidence of tracheotomy or non-invasive ventilation, ALS Functional Rating Scale, Quality of life and safety variables.

Inclusion Criteria:

• possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
• disease duration more than 6 months and less than 3 years
• best-sitting FVC between 50% and 95% of predicted normal
• continuously treated with 100 mg riluzole daily, for at least one month
• onset of progression weakness within 36 months prior to study
• women of childbearing age be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test
• capable of thoroughly understanding all information given and giving full informed consent according to GCP

Exclusion Criteria:

• previous participation in another clinical study within the preceding three months
• tracheotomy or assisted ventilation of any type during the preceding three months
• gastrostomy
• any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
• presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment
• confirmed hepatic insufficiency or abnormal liver function (ASAT and/or ALAT more than 1.5 upper limit of normal)
• renal insufficiency (serum creatinine more than 2.26 mg/dl)
• evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms
• known hypersensitivity to any component of the study drugs
• likely to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of an emergency
• other antidiabetics
• heart failure or heart failure in the patients history (NYHA I to IV)
• history of macular oedema
• treatment with thiazolidinediones within 3 months prior to screening
• known or suspected history of alcohol and/or drug abuse
• treatment with gemfibrozil within 3 months prior to screening