NCT00423228

Brief Summary

Alzheimer's disease is characterised by memory loss and difficulties with thinking. These problems may be due to a deficiency in a brain chemical called acetylcholine. Acetylcholine helps transmit messages between nerve cells. Acetylcholine is degraded by an enzyme called "acetylcholinesterase". ZT-1 is a new drug derived from a plant extract already used in China for memory disorders, which blocks the action of the enzyme and restores adequate levels of acetylcholine. This study will test the safety and efficacy of ZT-1 in the treatment of patients with Alzheimer's disease. BRAINz stands for Better Recollection for Alzheimer's patients with the Implant of ZT-1.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
228

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Feb 2007

Typical duration for not_applicable

Geographic Reach
3 countries

28 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 17, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 18, 2007

Completed
14 days until next milestone

Study Start

First participant enrolled

February 1, 2007

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2009

Completed
Last Updated

January 14, 2015

Status Verified

January 1, 2015

Enrollment Period

2.2 years

First QC Date

January 17, 2007

Last Update Submit

January 13, 2015

Conditions

Keywords

Alzheimer's diseasecognitive impairmentcholinesterase inhibitorssustained-release implantslong acting treatment

Outcome Measures

Primary Outcomes (1)

  • Change in the MMSE score from baseline to week 25

    baseline to week 25

Secondary Outcomes (5)

  • Responder rate as defined by at least 2 points improvement in the MMSE score;

    baseline to week 25

  • Change on the ADAS-Cog 11 items subscale;

    baseline to week 25

  • Change in the NPI-Q;

    baseline to week 25

  • Change on the IADL scale;

    baseline to week 25

  • Patient's convenience questionnaire.

    baseline to week 25

Study Arms (2)

ZT-1

EXPERIMENTAL

ZT-1 (investigational product)

Drug: ZT-1

Donepezil

ACTIVE COMPARATOR

Donepezil

Drug: Donepezil

Interventions

ZT-1DRUG

Patients in the ZT-1 treatment group will receive ZT 1-1 mg capsules administered p.o. daily during the first month of treatment, followed by ZT-1 implants (9 mg) administered s.c. during the second month of treatment, followed by ZT-1 implants (12 mg) administered s.c. every 4 weeks during months 3 to 6 of treatment. Patients in the ZT-1 treatment group will receive dummy donepezil capsules during months 2 to 6 of the treatment period.

ZT-1

Patients in the donepezil treatment group will receive donepezil 5 mg capsules administered p.o. during the first month of treatment, followed by donepezil 10 mg/day during months 2 to 6 of the treatment period. Patients in the donepezil treatment group will also receive s.c. injections of dummy ZT 1 implants every 4 weeks during months 2 to 6 of the treatment period.

Also known as: Aricept
Donepezil

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Presence of moderately severe probable AD, diagnosed according to the DSM-IV and the NINCDS-ADRDA criteria;
  • MMSE score ≥ 14 and ≤ 22;
  • Male/female patient aged \> 50 years; female patients should be of no child-bearing potential or postmenopausal (at least one year after last menses);
  • Body mass index (BMI) between 18 and 29 kg/m2 inclusive;
  • Has a caregiver, is living at home or in an assisted living facility, is able to attend ambulatory study visits;
  • Naïve to donepezil;
  • Has discontinued another AChEI and/or memantine at least 3 months prior to study visit 2 (Day 1);
  • Has a CT or MRI scan excluding another structural brain disease and supporting diagnosis of AD; CT or MRI scan must have been performed within 6 months prior to study visit 2 (Day 1, baseline);
  • Fluent in English (mother tongue or working language);
  • Able to communicate well with the Investigator;
  • Physically able to carry out functional tasks;
  • Has given written informed consent together with the caregiver.

You may not qualify if:

  • Presence of any disabling, severe or life-threatening disease (cardiac, respiratory, gastro-intestinal, neurological, epileptic, psychiatric, infectious, bone, endocrinologic);
  • Inability to discontinue at least 2 weeks prior to visit 2 (Day 1) (or within 5 drug half-lives, whichever is longer) any medication listed as prohibited;
  • Proven or clinically suspected other type of dementia such as vascular dementia, post-traumatic dementia, fronto-temporal dementia, dementia associated with Parkinson's Disease, infectious disease HIV, syphilis), folate or vitamin B12 deficiency, hypothyroidism etc.;
  • Significant liver impairment with ASAT, ALAT \>=3x the upper normal limit at screening;
  • Significant kidney impairment with serum creatinine \>=2x the upper normal limit at screening;
  • Presence of cardiac rhythm disorder, in particular bradycardia (\< 60 bpm), conduction abnormalities such as AV block; presence of active ischaemia (such as unstable angina pectoris) or recent myocardial infarction, QT interval ≥ 450 msec at screening, QRS complex ≥ 110 msec at screening (ECG must be within normal limits at screening);
  • Uncontrolled arterial hypertension i.e. patients with systolic blood pressure (BP) \>=160 mmHg and/or diastolic \>=100 mmHg, at screening despite regular medication;
  • Uncontrolled arterial hypotension, i.e. patients with systolic BP ≤ 100 mmHg and/or presenting a fall of systolic BP ≥ 20 mmHg or a fall of diastolic BP \>=10 mmHg after the 2 min Schellong test at screening;
  • Any concomitant disorder or resultant therapy that is likely to interfere with patient compliance or his/her participation to the study;
  • Participation in another study with an experimental drug within 3 months before study visit 2 (Day 1, baseline) or within 5 drug half-lives of the investigational drug (whichever is the longer);
  • Known peripheral cholinergic intolerance, i.e. with previously prescribed AChEI(s);
  • Known hypersensitivity to any of the test materials or related compounds, including lactose, present in the donepezil and placebo capsules;
  • Known active use of recreational drug or alcohol dependence, current alcohol abuse;
  • Inability to comply fully with the protocol;
  • Patients who, in the opinion of the Investigator, are considered unsuitable for any other reason.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

Central Coast Neuroscience Research

East Gosford, New South Wales, 2250, Australia

Location

Hornsby-Kuring-gai Health Service

Hornsby, New South Wales, 2077, Australia

Location

Southern Neurology

Kogarah, New South Wales, 2217, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

St George's Hospital

Kew, Victoria, 3101, Australia

Location

Austin Health Repatriation Hospital

West Heidelberg, Victoria, 3081, Australia

Location

Hollywood Specialist Centre

Nedlands (Perth), Western Australia, 6009, Australia

Location

Calgary West Medical Centre

Calgary, Alberta, T3C 3P1, Canada

Location

Castledowns Medicentre

Edmonton, Alberta, Canada

Location

Saibal Nandy Professional Corporation

Medicine Hat, Alberta, T1A 4C2, Canada

Location

Parkwood Hospital

London, Ontario, N6C 5J1, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2W7, Canada

Location

Gerontion Research Inc.

Toronto, Ontario, M6M 3Z5, Canada

Location

Neuro Rive-Sud

Montreal, Quebec, J4V 2J2, Canada

Location

Jewish General Hospital

Montreal, Quebec, P.Q. H3T 1E2, Canada

Location

The Medical Arts Health Research Group

Kelowna, V1Y 3G8, Canada

Location

Douglas Hospital Research Center

Montreal, H4H 1R3, Canada

Location

The Medical Arts Health Research Group

Penticton, V2A 5C8, Canada

Location

OPMHS

Crowborough, East Sussex, TN61HB, United Kingdom

Location

Camden and Islington Mental Health Trust

London, London, NW1 9DB, United Kingdom

Location

Glasgow Memory Clinic

Glasgow, Scotland, G20 0XA, United Kingdom

Location

Llandough Hospital

Penarth, Wales, CF64 2XX, United Kingdom

Location

Royal Blackburn Hospital

Blackburn, M8 5RB, United Kingdom

Location

North Manchester General Hospital

Manchester, M85RB, United Kingdom

Location

New Castle General Hospital

Newcastle upon Tyne, NE4 6BE, United Kingdom

Location

MARC - Moorgreen Hospital

Southampton, SO30 3JB, United Kingdom

Location

Related Publications (1)

  • Wilkinson D, Roughan L. The BRAINz trial: a novel approach to acetylcholinesterase-inhibitor treatment for Alzheimer's disease. Future Neurol 2(4):379-382,2007.

    BACKGROUND

Related Links

MeSH Terms

Conditions

Alzheimer DiseaseCognitive Dysfunction

Interventions

Donepezil

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental DisordersCognition Disorders

Intervention Hierarchy (Ancestors)

IndansIndenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPolycyclic Compounds

Study Officials

  • Emmanuel Tamches, MD

    Debiopharm SA

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 17, 2007

First Posted

January 18, 2007

Study Start

February 1, 2007

Primary Completion

April 1, 2009

Study Completion

April 1, 2009

Last Updated

January 14, 2015

Record last verified: 2015-01

Locations