Clinical trial NCT01354691: Safety and Efficacy Study of Ladostigil in Mild to Moderate Probable Alzheimer's Disease
Official title: A 6-Month Prospective, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Adaptive-Trial-Design Study to Evaluate the Safety and Efficacy of 80mg b.i.d Ladostigil in Patients With Mild to Moderate Probable Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Dementia
Memory Loss
Cognitive Impairment
Keywords: Alzheimer's Disease
Dementia
Memory Loss
Cognitive Impairment
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Depression
Anxiety
Lead sponsor: Avraham Pharmaceuticals Ltd
Sponsor class: INDUSTRY
First posted: 2011-05-17
Enrollment: 200
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: For many, Alzheimer's disease is the number one medical issue facing our aging society. It is a late onset neurodegenerative disease, frequently under diagnosed, that impairs memory and cognitive performance. There are no known treatments that can either prevent or reverse its progression. Consequently, there still remains a need to evaluate treatments which can better stabilize the symptoms of this disease. These symptoms frequently include decreased functional capacity and negative psychological attributes (e,g, depression, anxiety) in association with the memory and cognition deficits. This current study is being done to assess an investigational compound that has been designed to not only improved the cognitive status of affected patients but to also better manage all symptoms. Hence, the ultimate goal is to provide patients with an improved quality of life by slowing the progression of this neurodegenerative disease

Detailed description: This is a phase II, proof of concept study to evaluate the safety and efficacy of the investigational compound ladostigil versus placebo in mild to moderate Alzheimer's disease patients. The randomized, double-blind, placebo-controlled phase of the trial will be 26 weeks in duration and will involve two cohorts (i.e. one arm receiving ladostigil and one arm receiving placebo). After the initial 26 week period, all participating subjects will receive 26 weeks of treatment with ladostigil (i.e. the open label phase). A total of five territories will be participating in this trial. These include Austria, Croatia, Germany, Serbia and Spain.

Eligibility criteria: Inclusion Criteria:

* AD diagnosis according to NINCDS-ADRDA criteria
* Mild to moderate AD according to MMSE 14-24 inclusive
* MRI or CT assessment within 6 months before baseline, corroborating the clinical diagnosis and excluding other potential causes of dementia especially cerebrovascular lesions
* Absence of major depressive disease according to CSDD of less than or equal to 18
* Modified Hachinski Ischemic Scale equal to or below 4
* Education for eight or more years
* Previous decline in cognition for more than six months as documented in patient medical records
* A caregiver available and living in the same household or interacting with the patient daily and available if necessary to assure administration of investigational product
* Patients living at home or nursing home setting without continuous nursing care
* General health status acceptable for participation in a 12-month clinical trial and ability to swallow oral medication
* No history of treatment with rivastigmine
* For patients with either donepezil or galantamine anti-cholinesterase inhibitor treatment prescribed, stopped treatment four weeks prior to screening
* For patients with memantine treatment prescribed, stopped treatment four weeks prior to screening

Exclusion Criteria:

* Other primary degenerative dementias (e.g. dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Jacob-Creutzfeldt disease)
* Other neurodegenerative conditions (Parkinson's disease. amyotrophic lateral sclerosis, etc)
* Other central nervous system diseases (severe head trauma, tumors, subdural hematoma, etc)
* A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder
* Seizure disorders
* Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc)
* Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations
* Other unstable, chronic or clinically significant medical conditions involving major organs like kidney, liver, lungs and heart/vasculature
* Hospitalization or change of chronic concomitant medications one month prior to screening or during screening period

Primary outcomes:
measure: ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale
timeFrame: 26 weeks
Secondary outcomes:
measure: Neuropsychiatric Inventory (NPI)
timeFrame: 52 weeks
measure: Cornell Scale for Depression in Dementia (CSDD)
timeFrame: 52 weeks
measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: 52 weeks
measure: Mini-Mental State Examination
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medizinische Univeritat Graz, Universitatsklinik fur Neurologie, Auenbruggerplatz 22
city: Horn
country: Austria
facility: Privatordination Horn, HamerlingstraBe 15
city: Linz
country: Austria
facility: Allgemeines Krankenhaus der Stadt Linz, KrankenhausstraBe 9
city: Wein
country: Austria
facility: Privatordination, Lainzerstrasse 20
city: Pula
country: Croatia
facility: General Hospital Pula, Negrijeva 6
city: Zabok
country: Croatia
facility: General Hospital Zabok, Bracak 8
city: Zagreb
country: Croatia
facility: Clinical Hospital Center Zagreb, Kispaticeva 12
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava, Avenija Gojka Suska 6
city: Zagreb
country: Croatia
facility: Polyclinic Neuron, Salata 12
city: Zagreb
country: Croatia
facility: Psychiatric Hospital Vrapce, Bolnicka cesta 32
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg GmbH, Hoheluftaussee 18
city: Schwerin
country: Germany
facility: Klinische Forschung Schwerin GmbH, FriedrichstraBe 1
city: Westerstede
country: Germany
facility: Studienzentrum Nordwest, Lange StraBe 23-25
city: Belgrade
country: Serbia
facility: Military Medical Academy, Crnotravska 17
city: Belgrad
country: Serbia
facility: Clinical Centre of Serbia, Dr. Subotica 6
city: Algorta
country: Spain
facility: CAE Oroitu Centro Atencion Especializada C/Jata, 9
city: Barcelona
country: Spain
facility: Centro Geroinnova Barcelona, Calle Mandoni n 17
city: Barcelona
country: Spain
facility: Fundacio ACE, Institut Catala de Neurosciencies Aplicadas, C/Margues de Sentmenat 35-37
city: Salt
country: Spain
facility: Institud d' Assistencia Sanitaria de Girona, Edifici La Republica - C/Dr. Castany, s/n
Study officials:
affiliation: MEDIZINISCHE UNIVERSITAT GRAZ
name: Reinhold Schmidt, MD
role: PRINCIPAL_INVESTIGATOR
References: