The objectives of this study are to investigate the efficacy and safety of Nilvadipine as a disease course modifying treatment for mild to moderate AD in a phase III double-blind placebo-controlled study. substudy1 (frailty): the objectives of this…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy outcome measures in this study is the change from baseline
to week 78 in cognitive function, as assessed by the Alzheimer*s -Disease
Assessment Scale (ADAS -Cog 12). The analysis will take account of the
intermediate levels of this measure.
Substudy 1 (frailty): the change from baseline to week 78 in the frailty index
(if a statistically significant effect is seen the change to week 13 and 52
will be considered as co-primary)
Substudy 2 (research bloods): the change from baseline to week 78 in measured
biomarkers
Substudy 3 (CBF): the change from baseline to week 26 (with change to week 78
as a co-primary, when the change to week 26 is significant) in cerebral blood
flow, as assessed by pulsed Arterial Spin Labeling MRI
Secondary outcome
There are two key secondary outcome measures, the Clinical Dementia Rating
Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD).
If a statistically significant effect is seen in the primary outcome, CDR-sb
will be considered to be a co-primary endpoint and only the DAD will contribute
to the secondary outcome analysis.
Substudy 3 (CBF): the change from baseline to week 26 and to week 78 in:
-Blood pressure
-Blood pressure variability
-Cerebral autoregulation as measured by the dynamic relationship between: 1)
Blood pressure changes (Finapres), 2) Cerebral blood flow velocity, measured in
the middle cerebral artery (TCD), 3) Oxy/deoxy hemoglobin concentration in the
frontal cortex (NIRS)
-Orthostatic hypotension
-Vasomotor reactivity
-White matter integrity (MD/FA, measured with DTI)
-Regional CBF (ASL): frontal, temporal lobes and insula
Background summary
Alzheimer*s disease (AD) is an ever-increasing public health concern among the
aging population and is the most common form of dementia affecting more than 15
million individuals worldwide and around 5 million Europeans. The direct and
indirect costs of AD and other dementias amount to more than ¤440,000 million
each year (www.alz.org, 2010). It is estimated that by 2050, 1 in 85 of the
population worldwide will have AD and that approximately 40% of these cases
will need the level of care equivalent to a nursing home. Even modest
therapeutic advances that lead to small delays in Alzheimer*s onset and
progression could significantly reduce the global and European burden of the
disease and the level of care required by patients. While there are
symptomatic-based drug therapies available for AD, these medications do not
stop the disease process or prevent neuronal degeneration. There is therefore a
clear unmet medical and public health need for the development of new
treatments for AD that have disease modifying effects.
Study objective
The objectives of this study are to investigate the efficacy and safety of
Nilvadipine as a disease course modifying treatment for mild to moderate AD in
a phase III double-blind placebo-controlled study.
substudy1 (frailty): the objectives of this study is to investigate the
efficacy of Nilvadipine on the frailty index in patients who participate in
this NILVAD substudy.
substudy 2 (research bloods): the objectives of this study is to investigate
the genetic influences on the effect of Nilvadipine (through APOE4) and to
better understand the biological effects of Nilvadipine in humans by measuring
changes in biomarkers (amyloid, tau and inflammatory markers) in patients who
participate in this NILVAD substudy.
substudy 3 (CBF): the objectives of this study is to investigate the efficacy
of Nilvadipine on blood pressure, cerebral autoregulation, cerebral blood flow,
and -damage in patients who participate in this NILVAD substudy.
Study design
randomized double-blind placebo controlled parallel design
Intervention
Over encapsulated nilvadipine 8 mg, sustained release capsule, for the
treatment group, taken once a day at lunchtime or, matching over encapsulated
placebo for the control group, taken once a day at lunchtime.
Study burden and risks
Risk: Previous research showed that Nilvadipine is well tolerated by patients
with AD. Considering this finding and the low dosis of the medication we do not
expect a risk for the patient.
Burden: the study comprises 10 visits spread over 1,5 year. The visits are well
distributed over this period of time. We experience that patients find it
pleasant to regularly visit their doctor.
NOTE: the burden may increase if the patient chooses to participates in one or
more of the substudies. Further we will apply for an extra substudy for the
patients in Nijmegen, which results in more measurements.
Reinier Postlaan 4
NIJMEGEN 6525 GC
NL
Reinier Postlaan 4
NIJMEGEN 6525 GC
NL
Listed location countries
Age
Inclusion criteria
-prior diagnosis of mild to moderate AD based on NINCDS-ADRDA criteria
-age range: males and females over age 50 years.
-SMMSE score greather than or equal to 12, and less than 27
-stable dose (>3 months of cholinesterase inhibitor and or memantine). Subjects who are not on cholinesterase inhibitors or memantine due to poor tolerability and/or who will not require treatment with these medications during the course of the study can be included.
-Collateral informants such as a spouse, family member, close friend. The informant must have close contact with the subject and agree to monitor/manage study drug adherence, observe for possible adverse events, assist with psychometric measures requiring informant information, and accompany the subject to all evaluation visits.
-Fluency in relevant language sufficient to reliably complete all study assessments.
-Systolic BP between 100 mmHg and 159 mmHg, and diastolic BP between 65 mmHg and 99 mmHg on resting office based BP measurements, or a Systolic BP between 105 mmHg and 140 mmHg, and diastolic BP between 70 mmHg and 90 mmHg on ABPM measurement.
-written informed consent of patient and collateral informant
Exclusion criteria
-Diagnosis of significant neurological disease other than AD
-Subjects currently taking any calcium channel blocker or betablocker
-Subjects who in the opinion of the investigator, have a medical condition that would preclude them from participating in the study (e.g.hemodynamically significant coronary artery disease., chronic heart failure, syncope within the past year, significant valvular heart disease i.e. severe aortic and mitral stenosis.. symptomatic orthostatic hypotension within the last year, subjects requiring more than one agent to control BP.), or subjects who in the opinion of the investigator are unlikely to complete per protocol due to care issues etc.
-Current Axis I diagnosis of schizophrenia, bipolar disorder, major depression. Subjects who are currently or who have within the past year met criteria for drug or alcohol abuse or dependence.
-Subjects with a history of hypersensitivity to nilvadipine (Nivadil).
-Subjects who have taken an investigational or other unapproved drug during the 30 days or five half-lives, whichever is longer, prior to baseline.
(remaining, see protocol 4.3);substudy 3 (CBF): MRI-contra indication (metal implants, claustrophobia)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002764-27-NL |
| CCMO | NL40980.091.12 |