Dual Treatment With Lithium and Valproate in ALS.
Condition: Amyotrophic Lateral Sclerosis; Amyotrophic Lateral Sclerosis, Sporadic
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a pilot study in 40 subjects with definite ALS to evaluate the efficacy of valproate
      and lithium carbonate. After a random assignation of the dual treatment vs. placebo, a
      follow-up of 20 months will allow to know the clinical and functional evolution so as the
      status of biomarkers under each treatment.
    

Detailed description: 
      Amyotrophic lateral sclerosis (ALS) is a rare but fatal condition of the motor neuron.
      Despite intense therapeutic research in recent years, riluzole remains the only drug with
      proven efficacy in patients with this disease. In 2008 an Italian clinical-basic study
      reported benefits with lithium carbonate in both the experimental model of ALS and in a small
      sample of patients. In the same year, two Chinese studies showed a synergistic
      neuroprotective effect of valproate administered with lithium in neuronal cultures and in
      G93A ALS transgenic models.

      A clinical trial with lithium carbonate and magnesium valproate,conducted from 2009 to 2012
      in 18 patients with diagnostic criteria of ALS compared to a sample of 31 contemporary
      patients who did not receive the drug showed functionnal stability and an increase in
      antioxidant defenses in subjects under double treatment. Despite the low level of evidence
      from this open study, the combination of clinical and biological results as well as the
      significant increase in survival of treated subjects invites us to conduct a study yielding
      harsh results on the efficacy of dual treatment.

      To obtain harder data, the study will include 40 subjects with random assignation of the
      treatments (active vs. placebo) by electronic means. The development of the placebo tablets
      will be in charge of two pharmaceutical companies. Their delivery and purchase will be
      performed by a nursing team, the same team that will store and conserve the treatments. The
      preparation and packaging of the tablets for two months for 10 patients will be done
      regularly in a sterile environment. Two computer engineers will be in charge of the
      elaboration of the labels and the numerical draw of the treatments. The coordinator of the
      study will request the treatments in the nursing warehouse equipped with humidity and
      temperature control. Another person will be trained to make contacts, home deliveries, bottle
      changes and tablet counts. The appointments will be scheduled by the researchers every 2
      months as well as biosecurity exams and magnetic resonance studies in each patient within a
      20-month interval.

      This pilot study will allow the treatment efficacy to calculate the sample size required for
      the national and international multicenter clinical trial if relevant, to be promoted at the
      Mexican Academy of Neurology. It will also allow the study of the behavior of blood and MRI
      biomarkers ( SOD activity , DTI in cortico-spinal tract, and morphometric indexes).
    

Intervention name(s): Active treatment with dual therapy; Placebos
Intervention type(s): Combination Product; Drug
Intervention description(s): Blue pills ( 200 mg of magnesium valproate ) and white pills ( 300 mg of lithium carbonate) are administered orally with meals.; Administered orally under the same conditions
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Twenty ALS patients under active treatment vs. twenty ALS patients under placebo treatment. 21 months follow-up whith clinimetry and biomarkers
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Amyotrophic lateral sclerosis; Dual therapy; Randomized controlled trial; ALSFRS-R