Moderate Alzheimer's DiseaseBRAINzNCT00423228
Efficacy Study of a ZT-1 Implant in Patients Suffering From Alzheimer's Disease
A study testing ZT-1 and Donepezil in people with Moderate Alzheimer's Disease, run by Debiopharm International SA at 28 sites in 3 countries.
Trial 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". Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Moderate Alzheimer's Disease
- What is being tested?
- ZT-1 and Donepezil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 228 participants
- Where
- 28 sitesin 3 countries
- Study dates
- Feb 2007to Apr 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
28 sites in 3 countries.
28 sites in 3 countries
Canada11 sites
Calgary West Medical Centre
Calgary, Alberta, T3C 3P1
Castledowns Medicentre
Edmonton, Alberta
The Medical Arts Health Research Group
Kelowna, V1Y 3G8
Parkwood Hospital
London, Ontario, N6C 5J1
Saibal Nandy Professional Corporation
Medicine Hat, Alberta, T1A 4C2
Neuro Rive-Sud
Montreal, Quebec, J4V 2J2
Jewish General Hospital
Montreal, Quebec, P.Q. H3T 1E2
Douglas Hospital Research Center
Montreal, H4H 1R3
The Medical Arts Health Research Group
Penticton, V2A 5C8
Toronto Memory Program
Toronto, Ontario, M3B 2W7
Gerontion Research Inc.
Toronto, Ontario, M6M 3Z5
Australia9 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
The Prince Charles Hospital
Chermside, Queensland, 4032
Central Coast Neuroscience Research
East Gosford, New South Wales, 2250
Hornsby-Kuring-gai Health Service
Hornsby, New South Wales, 2077
St George's Hospital
Kew, Victoria, 3101
Southern Neurology
Kogarah, New South Wales, 2217
Hollywood Specialist Centre
Nedlands (Perth), Western Australia, 6009
Austin Health Repatriation Hospital
West Heidelberg, Victoria, 3081
The Queen Elizabeth Hospital
Woodville, South Australia, 5011
United Kingdom8 sites
Royal Blackburn Hospital
Blackburn, M8 5RB
OPMHS
Crowborough, East Sussex, TN61HB
Glasgow Memory Clinic
Glasgow, Scotland, G20 0XA
Camden and Islington Mental Health Trust
London, London, NW1 9DB
North Manchester General Hospital
Manchester, M85RB
New Castle General Hospital
Newcastle upon Tyne, NE4 6BE
Llandough Hospital
Penarth, Wales, CF64 2XX
MARC - Moorgreen Hospital
Southampton, SO30 3JB
About this study
Official title: A Randomised, Double-blind, Double-dummy, Oral Donepezil Controlled Study on the Safety and Efficacy of Repeated Monthly Subcutaneous Injections of a Sustained-release Implant of ZT 1 in Patients With Moderate Alzheimer's Disease
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.
Read the detailed description
This is a multicenter, randomised, double-blind, double-dummy, oral donepezil controlled study on the safety and efficacy of repeated monthly s.c. injections of a sustained-release implant of ZT 1 in patients with moderate Alzheimer's Disease.
The study enrolls patients aged >50 years, with moderate AD with a MMSE score at study screening ≥14 and ≤22. The study aims to recruit 128 patients.
The study is divided into 3 periods:
- A screening period
- A 6-month treatment period, consisting of one month of titration with an oral medication and 5 months of treatment with an implant administered under the skin every 4 weeks. Oral treatment will be maintained throughout the treatment phase
- A 2 week follow-up period.
Patients will be randomized in a 1:1 ratio to one of 2 groups: the ZT-1 (investigational product) treatment group or the donepezil (active comparator) treatment group.
The study comprises a total of 11 visits including screening and follow-up. An additional visit for PK/PD assessment is scheduled in about 10% of patients.
- Conditions
- Moderate Alzheimer's Disease
- Being tested
- ZT-1, Donepezil
- Keywords
- Alzheimer's disease, cognitive impairment, cholinesterase inhibitors, sustained-release implants, long acting treatment
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
DonepezilDrug
Also called Aricept
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.
| Study group | Role | What they receive |
|---|---|---|
| ZT-1 | Experimental | ZT-1 (investigational product) Receives: Drug: ZT-1 |
| Donepezil | Active comparator | Donepezil Receives: Drug: Donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the MMSE score from baseline to week 25
Measured: baseline to week 25
Secondary outcomes (5)
Responder rate as defined by at least 2 points improvement in the MMSE score;
Measured: baseline to week 25
Change on the ADAS-Cog 11 items subscale;
Measured: baseline to week 25
Change in the NPI-Q;
Measured: baseline to week 25
Change on the IADL scale;
Measured: baseline to week 25
Patient's convenience questionnaire.
Measured: baseline to week 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2007 (estimated)
- Study startFeb 2007
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Moderate Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 228 participants (actual)
Sponsor and investigators
- Lead sponsor
- Debiopharm International SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Emmanuel Tamches, MD, Study director, Debiopharm SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00423228
- Sponsor's protocol ID
- DEB-ZTSR-201
- Other IDs
- EUDRACT no. 2006-005161-18
- Acronym
- BRAINz
- Status last verified
- Jan 2015
- First submitted
- 17 Jan 2007
- Last updated
- 14 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Double-dummy, Oral Donepezil Controlled Study on the Safety and Efficacy of Repeated Monthly Subcutaneous Injections of a Sustained-release Implant of ZT 1 in Patients With Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT00423228
- Acronym / sponsor ID
- BRAINz / DEB-ZTSR-201
- Conditions
- Moderate Alzheimer's Disease
- Keywords
- Alzheimer's disease, cognitive impairment, cholinesterase inhibitors, sustained-release implants, long acting treatment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 228 participants (actual)
- Lead sponsor
- Debiopharm International SAIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 18 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, randomised, double-blind, double-dummy, oral donepezil controlled study on the safety and efficacy of repeated monthly s.c. injections of a sustained-release implant of ZT 1 in patients with moderate Alzheimer's Disease.
The study enrolls patients aged >50 years, with moderate AD with a MMSE score at study screening ≥14 and ≤22. The study aims to recruit 128 patients.
The study is divided into 3 periods:
- A screening period
- A 6-month treatment period, consisting of one month of titration with an oral medication and 5 months of treatment with an implant administered under the skin every 4 weeks. Oral treatment will be maintained throughout the treatment phase
- A 2 week follow-up period.
Patients will be randomized in a 1:1 ratio to one of 2 groups: the ZT-1 (investigational product) treatment group or the donepezil (active comparator) treatment group.
The study comprises a total of 11 visits including screening and follow-up. An additional visit for PK/PD assessment is scheduled in about 10% of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZT-1 | Experimental | Drug: ZT-1ZT-1 (investigational product) |
| Donepezil | Active comparator | Drug: DonepezilDonepezil |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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;
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZT-1Patients 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. | Drug | ZT-1 |
| DonepezilAlso: AriceptPatients 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. | Drug | Donepezil |
Primary outcome
Change in the MMSE score from baseline to week 25
Time frame: baseline to week 25
5 secondary outcomes
Responder rate as defined by at least 2 points improvement in the MMSE score;
Time frame: baseline to week 25
Change on the ADAS-Cog 11 items subscale;
Time frame: baseline to week 25
Change in the NPI-Q;
Time frame: baseline to week 25
Change on the IADL scale;
Time frame: baseline to week 25
Patient's convenience questionnaire.
Time frame: baseline to week 25
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2015.
- BackgroundWilkinson D, Roughan L. The BRAINz trial: a novel approach to acetylcholinesterase-inhibitor treatment for Alzheimer's disease. Future Neurol 2(4):379-382,2007.
- Sponsor of the StudyLink provided by the sponsor.
- Alzheimer's Disease Education and Referral (ADEAR) CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanuel Tamches, MD study director
Debiopharm SA
28 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ZT-1 and Donepezil in people with Moderate Alzheimer's Disease, run by Debiopharm International SA at 28 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Canada, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the MMSE score from baseline to week 25 (time frame: baseline to week 25). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00423228, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2015.