Dual Treatment With Lithium and Valproate in ALS.
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|ClinicalTrials.gov Identifier: NCT03204500|
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : February 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis, Sporadic||Combination Product: Active treatment with dual therapy Drug: Placebos||Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|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)|
|Masking Description:||This is a prospective randomized double-blind placebo-controlled trial. The randomization is made in blocks of 4 treatments (2 active and 2 placebo). Only the 4-digit numbers on the bottle label will identify the type of treatment.|
|Official Title:||A Randomized Clinical Trial, Double Blind, Placebo-controlled of Lithium and Valproate in Amyotrophic Lateral Sclerosis.|
|Actual Study Start Date :||May 2016|
|Estimated Primary Completion Date :||April 2018|
|Estimated Study Completion Date :||June 2018|
Experimental: Active treatment with dual therapy
This group is composed by 20 ALS subjects under 600mg valproate and 600 mg of litium carbonate per day, during 21 months. The tablets are given orally with meals.
Combination Product: Active treatment with dual therapy
Blue pills ( 200 mg of magnesium valproate ) and white pills ( 300 mg of lithium carbonate) are administered orally with meals.
Placebo Comparator: placebos
This group is composed by 20 ALS subjects under placebo. Blue tablets ( placebo of VPA) and white tablets (placebo of Li) are administered under the same conditions.
Administered orally under the same conditions
- Changes in ALSFRS-R [ Time Frame: Every 2 months for 20 months ]To evaluate the effect of VPA+Li on progression of ALS by measuring functionnal changes from baseline in ALSFRS-R.
- Changes in score in ALSAQ-5 [ Time Frame: Baseline, Month 10, Month 20 ]Changes from baseline in ALSAQ-5, a brief self-administered quality of life scale.
- Changes from baseline in FA (fractional anisotropy) [ Time Frame: Baseline and month18 ]DTI biomarkers in corticospinal tract are measured in 6 regions bilaterally
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03204500
|Instituto Nacional de Neurologia Y Neurocirugia Mvs|
|Mexico City, Distrito Federal, Mexico, 14269|
|Principal Investigator:||MARIE CATHERINE BOLL, MD,PhD.||525556063822|