NCT01429623

A 3 Year Study to Evaluate the Safety and Efficacy of Low Dose Ladostigil in Patients With Mild Cognitive Impairment

A 36-month, Multi-centre, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Low Dose Ladostigil in Patients With Mild Cognitive Impairment (MCI)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 210 (actual)
• Sponsor: Avraham Pharmaceuticals Ltd · Industry
• Sex: All
• Age: 55 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether treatment with the investigational drug ladostigil will delay the onset of Alzheimer's disease(AD) in patients with Mild Cognitive Impairment (MCI). MCI is now recognized as a precursor to AD and clinical tools are available to assess cognitive performance at this earlier stage. Ladostigil is currently under investigation for the treatment of AD. In this study, the investigators will be examining ladostigil at a lower dose level. At this dose level, ladostigil has been shown to reduce signs of early memory loss in animals. Thus, in this study the investigators are attempting to determine if earlier invention with a lower dose of ladostigil will significantly reduce initial memory loss and delay the subsequent progression to more serious cognitive dysfunction.

Detailed description

Ladostigil shows neuroprotective activity, reducing oxidative stress, activating microglia, and inhibiting pro-inflammatory cytokines in pre-clinical models. Study assessed its safety and potential efficacy in a 3-year, randomised, double-blind, placebo-controlled, phase 2 clinical trial in patients with mild cognitive impairment (MCI). Patients from 16 centers in Austria, Germany and Israel with MCI (Albert et al 2011), Clinical Dementia Rating (CDR) = 0.5, Mini-Mental State Examination (MMSE) \> 24, Wechsler Memory Scale - Revised Verbal Paired Associates ≤ 18, and medial temporal lobe atrophy were stratified by APOE4 genotype and randomly assigned (1:1 allocation) using blocks of 4, to receive either ladostigil, 10 mg per day, or placebo as identically-appearing capsules. The primary endpoint was onset of Alzheimer's disease (AD). Secondary endpoints were the NTB, DAD, and GDS. Exploratory outcomes were MRI-derived whole brain, hippocampus, and entorhinal cortex volumes; the NeuroTrax Mindstreams computerized cognitive battery; and the CDR. Between February 17, 2012 and August 1, 2013, we randomly allocated 210 patients to placebo (107 patients) or ladostigil (103 patients); 4 patients in each group lacked post baseline assessments. After 36 months 20.4% (21 of 103 patients) of the placebo group and 14.1% (14 of 99 patients) of the ladostigil group progressed to AD (log-rank test p=.16). There were no significant effects on NTB, DAD, or GDS outcomes. There was less decline in whole brain volume in the ladostigil group as compared to placebo (p\<.02), but not hippocampus and entorhinal cortex volumes, and CDR and a trend for less decline on the RAVLT total delayed score component of the NTB (p=.09). Fourteen patients taking placebo and 21 taking ladostigil discontinued treatment because of adverse events. Serious adverse events were reported by 26 (25.2%) patients in the ladostigil group and 28 (26.2%) patients in the placebo group. Ladostigil appeared safe, well-tolerated, and may have potential for improving memory and delaying progression to dementia.

Conditions

• Mild Cognitive Impairment
• Dementia

Interventions

Type	Name	Description
DRUG	ladostigil hemitartrate	10mg ladostigil base administered once daily as hard gelatin capsule
DRUG	Placebo	Placebo comparator

Timeline

• Start date: 2012-02-01
• Primary completion: 2016-07-01
• Completion: 2016-09-01
• First posted: 2011-09-07
• Last updated: 2017-06-15
• Results posted: 2017-06-15

Locations

12 sites across 3 countries: Austria, Germany, Israel