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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Comparative Study to Test Safety and Efficacy of Neurotrophic and Cholinergic Treatment of Alzheimer's Disease

Short name Combi

Overview

Status
Completed
Phase
Phase 2
Enrollment
217 participants (actual)
Sponsor
Ever Neuro Pharma GmbH · Industry
Design
Randomized · Quadruple masking
Countries
1 country

Spain

Start
Oct 2004
Primary completion
Apr 2008
Completion
Apr 2008
First posted
2 Jun 2009 (estimated)
Last update posted
10 Jun 2009 (estimated)
Conditions
Alzheimer Disease

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
200420052006200720082009
  1. Ph 2

    Combi

    NCT00911807

    Oct 2004 to Apr 2008

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The study was performed to compare the safety and efficacy of Cerebrolysin (10 mililiters \[ml\]), Aricept (10 miligrams \[mg\]), and a combination of both treatments on cognitive performance and global function in patients with probable Alzheimer's Disease (AD). It should also be assessed if the treatments have a positive effect on activities of daily living and neuropsychiatric symptoms. Oral treatment with Aricept or Placebo was given once daily throughout the study. Intravenous treatment with Cerebrolysin or Placebo was given once daily for 5 days per week during week 1 to 4 and during week 13 to 16 of the study. During the study patients had six visits at the hospital for evaluation.

Interventions

  • Cerebrolysin + donepezilDrug
  • Cerebrolysin + placeboDrug
  • Donepezil + placeboDrug

Arms3

  • Experimental

    Cerebrolysin + donepezil

  • Experimental

    Cerebrolysin + placebo

  • Active comparator

    Donepezil + placebo

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive Subpart (Extended Version) (ADAS-COG+) at Week 28

    Time frame · baseline and week 28

    Registry description

    The ADAS-cog+ is a validated, widely used, 14 item psychometric instrument for testing cognitive functions with increased sensitivity in detecting changes in milder patients compared to the original ADAS-cog. It has a maximum score of 85 with a higher score indicating impairment and was assessed by a qualified neuropsychologist.

  2. Clinical Interview-based Impression of Change (CIBIC+) Score

    Time frame · week 28

Secondary outcomes(10)
  1. Change From Baseline for ADAS-COG+

    Time frame · week 4, 12, 16

  2. ADAS-COG+ Responders

    Time frame · week 4, 12, 16, 28

  3. Change From Baseline for Original ADAS-COG

    Time frame · week 4, 12, 16, 28

  4. CIBIC+ Score

    Time frame · week 4, 12, 16

  5. CIBIC+ Responders

    Time frame · week 4, 12, 16, 28

  6. Clinical Interview-based Impression of Severity (CIBIS+) Score

    Time frame · week 28

  7. Change From Baseline for Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)

    Time frame · week 16, 28

  8. Change From Baseline in Total Score for Neuropsychiatric Inventory (NPI)

    Time frame · week 16, 28

  9. Combined Responders, i.e. Response in ADAS-COG+ and CIBIC+

    Time frame · week 4, 12, 16, 28

  10. Adverse Experiences, Vital Signs, Physical and Neurological Examinations, Laboratory Tests (Hematology, Clinical Chemistry , Urinalysis, Electrocardiogram [ECG])

    Time frame · Baseline, week 4, 12, 16, 28

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· baseline and week 28

Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive Subpart (Extended Version) (ADAS-COG+) at Week 28

GroupValue (points on a scale)Spread
Cerebrolysin + Donepezil-2.3485.993
Cerebrolysin-1.7117.500
Donepezil-1.2466.147
Primary outcome· week 28

Clinical Interview-based Impression of Change (CIBIC+) Score

GroupValue
Secondary and other outcome results(6)
Secondary outcome· week 4, 12, 16

Change From Baseline for ADAS-COG+

GroupValue
Secondary outcome· week 4, 12, 16, 28

ADAS-COG+ Responders

GroupValue
Secondary outcome· week 4, 12, 16, 28

Change From Baseline for Original ADAS-COG

GroupValue
Secondary outcome· week 4, 12, 16

CIBIC+ Score

GroupValue
Secondary outcome· week 4, 12, 16, 28

CIBIC+ Responders

GroupValue
Secondary outcome· week 28

Clinical Interview-based Impression of Severity (CIBIS+) Score

GroupValue

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Cerebrolysin + Donepezil–1 / ?45 / ?
Cerebrolysin–1 / ?40 / ?
Donepezil–2 / ?46 / ?

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2011

14 results

Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with cerebrolysin and donepezil.

Alvarez et al. 2011Current Alzheimer researchcited by 38

PMID 21679156DOI 10.2174/156720511796391863PUB-21679156

Full text at the publisher14 results

Eligibility

Who could join, as posted.

Sex
All
Age
from 51 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria * Diagnosis of probable AD (Diagnostic and Statistical Manual of Mental Disorders, 4th revision \[DSM-IV\], National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association \[NINCDS-ADRDA\]) * Mini-Mental-State-Examination (MMSE) of 12-25, inclusive * Modified Hachinski score ≤4 * Computed tomography (CT) or magnetic resonance imaging (MRI) scan within 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. Patients who have had a single, clinically silent lacunar infarct are eligible provided the lacunar infarct is not felt to be responsible for the patient's symptoms, is \<1 centimeter (cm) maximal diameter in any dimension, is not present in hippocampus of either hemisphere, head of the left caudate, or the dorsomedial region of the left thalamus. Subjects with scans showing atrophy, ventricular enlargement or mild to moderate white matter changes (involving up to approximately 25% of hemispheric white matter) are eligible if the study is otherwise normal. * Hamilton Depression Scale score of ≤15 * Adequate visual and auditory acuity to allow neuropsychological testing * Ability to attempt all sections of the Alzheimer's Disease Assessment Scale Cognitive Subpart (extended version)(ADAS-cog+) * Good general health without additional diseases expected to interfere with the study * Normal B12, folic acid, venereal disease research laboratory (VDRL), and thyroid-stimulating hormone (TSH) or without any clinically significant laboratory abnormalities that would be expected to interfere with the study * Electrocardiogram (ECG) and chest x-ray (if clinically necessary per Investigator) without clinically significant laboratory abnormalities that would be expected to interfere with the study * Patient is not institutionalized * Patient is not pregnant, lactating, or of childbearing potential * Sufficient language skills to complete all testing without assistance of a language interpreter * Responsible caregiver being present during administration of study drug, monitor the patient's compliance with study procedures and adverse events, and accompany the patient to all clinic visits * Written informed consent obtained from the patient and caregiver prior to entry into the study Exclusion criteria * Any clinically significant laboratory abnormalities on the battery of screening tests * Patients who in the past have not tolerated treatment with 10 mg Aricept or treatment with a corresponding dose of another cholinesterase inhibitor * Severe psychotic features, depression, agitation or behavioral problems within the last three months that could lead to difficulty complying with the protocol * Any significant systemic illness or unstable medical condition that could lead to difficulty complying with the protocol * Patients who in the Investigator's opinion would not comply with study procedures * Any significant neurological disease other than Alzheimer's Disease, within the past five years, or with residual effects * Delusional symptoms are often characteristic of Alzheimer's Disease, but patients with symptoms so pronounced that they warrant an alternative diagnosis are excluded * History of alcohol or substance abuse or dependence within the past two years (DSM-IV) * History of schizophrenia (DSM-IV) * Patients with a history of systemic cancer within the past two years are excluded * History of myocardial infarction in the past year or unstable or severe cardiovascular disease, including uncontrolled hypertension * Uncontrolled insulin-requiring diabetes or non-insulin dependent diabetes mellitus (Haemoglobin A1c \[HBA1c\] \> 10.0) * Use of: * systemic corticosteroids for more than one week within three months prior to Baseline (BL) * Anti-Parkinsonian agents within two months prior to baseline (BL) * Approved or investigational Cholinesterase Inhibitors within 30 days or five half-lives, whichever is longer, prior to BL * Memantine or other N-methyl-D-aspartic acid (NMDA) antagonists within 30 days or five half-lives, whichever is longer, prior to BL * Treatment with high potency neuroleptics or narcotic analgesics within four weeks prior to BL * Cimetidine within four weeks prior to BL * Sedatives more frequently than two times per week for sleep within four weeks prior to BL

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