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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
Göteborg University
University College Cork
Aristotle University Of Thessaloniki
Stichting Katholieke Universiteit
Information provided by (Responsible Party):
Prof Brian Lawlor, St. James's Hospital, Ireland

Tracking Information
First Submitted Date  ICMJE December 16, 2013
First Posted Date  ICMJE December 20, 2013
Last Update Posted Date March 6, 2017
Actual Study Start Date  ICMJE April 24, 2013
Actual Primary Completion Date December 16, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2013)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Trial of Nilvadipine to Treat Alzheimer's Disease
Official Title  ICMJE A European Multicentre Double-blind Placebo-controlled Phase III Trial of Nilvadipine in Mild to Moderate Alzheimer's Disease
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.

Detailed Description Please see 'Brief Summary', above
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Nilvadipine
    8mg of Nilvadipine taken once a day at lunch time for 78 weeks
    Other Name: Also known as Nilvadil (Brand Name)
  • Drug: Placebo
    8mg Placebo tablet taken once a day at lunch time for 78 weeks
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    250 patients will receive the placebo
    Intervention: Drug: Placebo
  • Active Comparator: Nilvadipine
    250 patient will receive the active drug Nilvadipine 8mg
    Intervention: Drug: Nilvadipine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 3, 2017)
511
Original Estimated Enrollment  ICMJE
 (submitted: December 16, 2013)
500
Actual Study Completion Date  ICMJE December 16, 2016
Actual Primary Completion Date December 16, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Greece,   Hungary,   Ireland,   Italy,   Netherlands,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02017340
Other Study ID Numbers  ICMJE NILVAD2012
2012-002764-27 ( EudraCT Number )
279093 ( Other Grant/Funding Number: European Commission Framework Programme )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Prof Brian Lawlor, St. James's Hospital, Ireland
Study Sponsor  ICMJE Prof Brian Lawlor
Collaborators  ICMJE
  • 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
  • Göteborg University
  • University College Cork
  • Aristotle University Of Thessaloniki
  • Stichting Katholieke Universiteit
Investigators  ICMJE
Principal Investigator: Brian Lawlor, Prof University of Dublin, Trinity College
PRS Account St. James's Hospital, Ireland
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP