Efficacy of Ladostigil to treat patients with Mild Cognitive Impairment.

Phase 1

• Conditions: Patient with Mild Cognitive Impairment; MedDRA version: 19.0Level: LLTClassification code 10009846Term: Cognitive impairmentSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2011-004187-30-AT
• Lead Sponsor: Avraham Pharmaceuticals Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-11-14
• Last Update Posted: 29 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Men and women (non-childbearing potential) with a diagnosis of MCI according to consensus criteria as defined by Petersen and according to NIA recommendations.
2. Abnormal memory function will be evaluated by Verbal Paired Associates from the Wechsler Memory Scale – Revised. Normal values for healthy adults in two age cohorts are: a) 50-70 years 19.7 (SD = 2.9) and b) 75-95 years 18.3 (SD = 2.8). Patients that score = 18 will be included.
3. Clinical Dementia Rating (CDR) score of 0.5 (Memory box score 0.5 or 1, no box score greater than 1).
4. Mini-Mental State Examination (MMSE) > 24.
5. General cognition and functional performance sufficiently preserved such that a diagnosis of AD can be excluded by the site physician at the time of the screening visit.
6. No significant cerebrovascular disease indicated by Modified Hachinski Ischaemic Score equal to or below 4.
7. Age 55 - 85 years, because no significant correlation of cognition and Schelten's score has been observed above the age of 85.
8. Geriatric Depression Scale (GDS) of less than or equal to 5.
9. An available informer who has frequent contact with the subject (e.g. an average of 10 hours per week or more) who will agree to monitor administration of study drug, to observe the subject for adverse events, and to accompany the subject to clinical visits during the trial, if the presence of the informer is required.
10. All patients will need to undergo an MRI scan after the screening visit, i.e. during the screening period, irrespective of MRIs having been performed prior to entry into the study. MRI findings have to be consistent with a diagnosis of MCI.
11. Central rating of medial temporal lobe according to Schelten's scale [3]. The right and left medial temporal structures will be rated separately, and an overall estimate will be created using the average of the two ratings [5]. An average score > 1 is required to make patients eligible for the study.
12. Adequate visual and auditory acuity must be given to allow neuropsychological testing.
13. Good general health status acceptable for a participation in a 36-month clinical trial, with no additional diseases expected to interfere with the study.
14. ECG without clinically significant abnormalities
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Failure to perform screening or baseline examinations.
2. Any significant neurologic disease other than suspected MCI.
3. MRI exclusion criteria which allow for mild concomitant vascular lesions are:
- Thromboembolic infarction
- Other focal lesions which may be responsible for the cognitive status of the patient such as infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with significant central nervous disease.
- More than one lacunar infarct defined as a focal lesion of CSF signal intensity with a diameter of less than 1.5 cm in any dimension.
- Any lacunar infarct in a strategically important location such as the thalamus, hippocampus of either hemisphere, head of the left caudate.
- White matter lesions involving more than 25% of the hemispheric white matter.
- Implants such as pacemakers, insulin pumps, cochlear implants, nerve stimulators, implantable cardioverter defibrillators, and other medical implants that have not been certified for MRI.
- Ferromagnetic foreign bodies such as shell fragments need to be considered on an individual basis
- Metallic implants that can cause artifacts and RF induced heating such as surgical prostheses or aneurysm clips need to be considered on an individual basis
4. Clinical or laboratory findings consistent with:
- Central nervous system diseases such as those resulting from severe head trauma, tumours, subdural haematoma or other space occupying processes, etc.
- Seizure disorder.
- 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.)
5. History or evidence of schizophrenia or bipolar disorder (DSM IV criteria ). Active major depression.
6. Clinically significant advanced or unstable diseases that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:
- Malignant tumours with the last five years except skin malignancies (other than melanoma) or indolent prostate cancer
- Metastases
- History of myocardial infarction within one year prior to screening or unstable or severe cardiovascular disease including angina or congestive heart failure with symptoms at rest.
- Uncontrolled hypertension (systolic pressure > 170 mmHg or diastolic pressure > 100 mmHg).
- Bradycardia (persistent heart beat < 50/min) or tachycardia (persistent heart beat > 100/min) at rest.
- AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males > 450 msec, females > 470 msec)
- Clinically significant obstructive pulmonary disease or asthma.
- Clinically significant laboratory findings that indicate abnormalities in blood biochemistry, blood haematology or urinalysis.
- Uncontrolled diabetes mellitus defined by HbA1c > 8.5.
- Clinically significant liver disease, coagulopathy, or vitamin K deficiency within the past two years prior to screening.
- Renal insufficiency (serum creatinine >2mg/dl or creatinine clearance = 45 mL/min according to Cockgroft-Gault formula). In case of creatinine clearance =45mL/min, an alternative verification of the renal function must be completed using cystatin C analysis. In case of normal level of cystatin C the patient can be includ

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified