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A Phase III Trial of Nilvadipine to Treat Alzheimer's Disease (NILVAD)

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ClinicalTrials.gov Identifier: NCT02017340
Recruitment Status : Completed
First Posted : December 20, 2013
Last Update Posted : March 6, 2017
Sponsor:
Collaborators:
University of Dublin, Trinity College
Molecular Medicine Ireland LBG
Alzheimer Europe
Archer Pharmaceuticals, Inc.
E-Search Limited
University College Dublin
King's College London
Istituto Di Ricerche Farmacologiche Mario Negri
University Hospital, Lille
University of Ulm
Szeged University
Goeteborgs Universitet
University College Cork
Aristotle University Of Thessaloniki
Stichting Katholieke Universiteit
Information provided by (Responsible Party):
Prof Brian Lawlor, St. James's Hospital, Ireland

Brief 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).

Even modest therapeutic advances that delay disease onset and progression could significantly reduce the global 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 prevent the disease process itself. There is therefore an imperative to develop new treatments for AD that have disease modifying effects. This double-blind placebo controlled study will test the efficacy and safety of nilvadipine in 500 subjects with mild to moderate AD over a treatment period of 18 months. There is a strong scientific rationale for this study: Nilvadipine, a licensed calcium channel enhances Aß clearance from brain and restores cortical perfusion in mouse models of AD. Nilvadipine is safe and well tolerated in AD patients and clinical studies with this medication have shown stabilization of cognitive decline and reduced incidence of AD, pointing to both symptomatic and disease modifying benefits. Male and female patients with mild to moderate AD aged between 50 and 90 with a range of medical morbidities and frailty will be included in the study. If this trial is successful, nilvadipine would represent an advance in the treatment of AD patients and would have a major impact on the health and social care costs incurred in Europe by this neurodegenerative disorder. Furthermore, the creation of the NILVAD network will support future clinical trials and research innovation in AD across Europe.


Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Nilvadipine Drug: Placebo Phase 3

Detailed Description:
Please see 'Brief Summary', above

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 511 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A European Multicentre Double-blind Placebo-controlled Phase III Trial of Nilvadipine in Mild to Moderate Alzheimer's Disease
Actual Study Start Date : April 24, 2013
Actual Primary Completion Date : December 16, 2016
Actual Study Completion Date : December 16, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
250 patients will receive the placebo
Drug: Placebo
8mg Placebo tablet taken once a day at lunch time for 78 weeks

Active Comparator: Nilvadipine
250 patient will receive the active drug Nilvadipine 8mg
Drug: Nilvadipine
8mg of Nilvadipine taken once a day at lunch time for 78 weeks
Other Name: Also known as Nilvadil (Brand Name)




Primary Outcome Measures :
  1. Alzheimer's Disease Assessment Scale (ADAS) Cog [ Time Frame: 18 months ]
    The Alzheimer's Disease Assessment Scale (Cognitive) (Mohs et al. 1983) ADAS-cog 12 is a primary efficacy outcome measure, and includes 12 items of cognitive evaluation, namely immediate word recall, naming objects and fingers, commands, constructional praxis, ideational praxis, orientation, word recognition, remembering test instructions, spoken language ability, word-finding difficulty in spontaneous speech, comprehension & delayed recall. A higher ADAS-cog score indicates a poorer cognitive function.


Secondary Outcome Measures :
  1. Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) [ Time Frame: 18 months ]
    Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) (Morris et al 1993) is the secondary efficacy outcome measure. This is a semi-structured interview with the caregiver and the patient. The patient's performance in the domains of memory, orientation, judgment, problem solving, community affairs, home and hobbies and personal care are assessed. The CDR-sb is scored from 0-18, with the higher score indicated greater impairment.

  2. Disability Assessment for Dementia (DAD) [ Time Frame: 18 months ]
    Disability Assessment for Dementia (DAD) (Gelinas et al. 1999) is a key secondary efficacy outcome measure and evaluates the basic and instrumental activities in daily activities of elderly people with dementia. This 40-item scale addresses a range of functional domains: eating, meal preparation, telephoning, hygienic, dressing, medication, corresponding, finance, leisure, and housework.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age range: Adult subjects, males and females over age 50 years.
  2. Prior diagnosis of mild to moderate probable AD based on NINCDS-ADRDA criteria (see Appendix B) and
  3. Standardised Mini-Mental State Examination (SMMSE) score > 12 on 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.
  4. 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.
  5. Fluency in relevant language sufficient to reliably complete all study assessments.
  6. Systolic BP > 100 mmHg but ≤ 159 mmHg, and diastolic BP > 65 mmHg but ≤ 99 mmHg on resting office based BP measurements, or a Systolic BP > 105 mmHg but ≤ 140 mmHg, and diastolic BP > 70 mmHg but ≤ 90 mmHg on ABPM measurement

Exclusion Criteria:

  1. Subjects with co-morbid dementia due to other neurological disorders such as Parkinson's disease, vascular dementia, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, or multiple sclerosis, as well as subjects with HIV disease, neurosyphilis, history of significant head trauma with loss of consciousness followed by persistent neurological deficits, known structural brain abnormalities, or any other condition known to interfere with cognitive function.
  2. Subjects currently taking any calcium channel blocker or Beta-blocker
  3. 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:
  4. 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.
  5. Pregnant women or women who may possibly become pregnant.
  6. Subjects with a history of hypersensitivity to nilvadipine (Nivadil).
  7. Subjects who have taken an investigational or other unapproved drug during the 30 days or five half-lives, whichever is longer, prior to baseline.
  8. Subjects who are participating in other research studies.
  9. Patients with a SBP of ≤ 100 mmHg and/or a DBP of ≤ 65 mmHg on office based BP measurements, or a SBP ≤ 105 mmHg and/or a DBP of ≤ 70 mmHg on ABPM will not be included in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02017340


Locations
France
Centre Hospitalier Universitaire d'Amiens (CHU Amiens)
Amiens, France
Centre Hospitalier Universitaire de Bethune (CH Bethune)
Bethune, France
Centre Hospitalier Universitaire de Caen (CHU Caen)
Caen, France
Centre Hospitalier Universitaire de Calais (CHU Calais)
Calais, France
Centre Hospitalier Universitaire de Lens (CHU Lens)
Lens, France
Centre Hospitalier Regional et Universitaire de Lille (CHRU Lille)
Lille, France
Centre Hospitalier Universitaire de Saint Philibert (GHICL)
Lille, France
Germany
University of Ulm
Ulm, Germany
Greece
"G. Papanicolaou" Hospital
Athens, Greece
"G.Papageorgiou" Hospital
Athens, Greece
AXEPA Hospital
Athens, Greece
Hungary
Szeged University
Szeged, Hungary
Ireland
University College Cork
Cork, Ireland
St James Hospital
Dublin, Ireland
Italy
Hospital of Brescia
Brescia, Italy
Hospital Castellanza
Castellanza, Italy
Hospital of Genoa
Genoa, Italy
Hospital of Milan
Milan, Italy
Netherlands
Hospital of Arnhem
Arnhem, Netherlands
Hospital of Maastricht
Maastricht, Netherlands
Hospital of Nijmegen
Nijmegen, Netherlands
Sweden
Gothenburg Univeristy
Gothenburg, Sweden
United Kingdom
Kings College London
London, United Kingdom
Sponsors and Collaborators
Prof Brian Lawlor
University of Dublin, Trinity College
Molecular Medicine Ireland LBG
Alzheimer Europe
Archer Pharmaceuticals, Inc.
E-Search Limited
University College Dublin
King's College London
Istituto Di Ricerche Farmacologiche Mario Negri
University Hospital, Lille
University of Ulm
Szeged University
Goeteborgs Universitet
University College Cork
Aristotle University Of Thessaloniki
Stichting Katholieke Universiteit
Investigators
Principal Investigator: Brian Lawlor, Prof Trinity College Dublin

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof Brian Lawlor, Project Coordinator, St. James's Hospital, Ireland
ClinicalTrials.gov Identifier: NCT02017340     History of Changes
Other Study ID Numbers: NILVAD2012
2012-002764-27 ( EudraCT Number )
279093 ( Other Grant/Funding Number: European Commission Framework Programme )
First Posted: December 20, 2013    Key Record Dates
Last Update Posted: March 6, 2017
Last Verified: March 2017

Keywords provided by Prof Brian Lawlor, St. James's Hospital, Ireland:
Alzheimer's Disease
Investigator-driven clinical trial
Nilvadipine
Calcium Channel blocker
Elderly
Therapeutic Intervention

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Nilvadipine
Nifedipine
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs