A Non-drug Methods Study in Patients With Alzheimer's Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01459016
First received: October 12, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

This study will investigate the volume, function and composition of the brain using magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning technology in participants with memory complaints or early signs of Alzheimer's pathology.


Condition Intervention Phase
Alzheimer's Disease
Other: PET scan using florbetapir
Other: MRI Scan
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Exploratory Study of Brain Imaging Biomarkers in Patients With Alzheimer's Pathology Receiving Standard of Care

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change from baseline up to 9 months in volumetric magnetic resonance imaging (vMRI) [ Time Frame: Time zero equals baseline, up to 9 months ] [ Designated as safety issue: No ]
  • Change from baseline up to 9 months in resting state functional magnetic resonance imaging (rsfMRI) [ Time Frame: Time zero equals baseline, up to 9 months ] [ Designated as safety issue: No ]
  • Change from baseline up to 9 months in diffusion tensor imaging (DTI) [ Time Frame: Time zero equals baseline, up to 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Baseline brain amyloid load using Positron Emission Tomography (PET) and florbetapir [ Time Frame: Time zero equals baseline ] [ Designated as safety issue: No ]
  • Number of participants with vasogenic edema on MRI scan at a field strength of 3T [ Time Frame: Time zero equals baseline, up to 9 months ] [ Designated as safety issue: No ]
  • Number of participants with microhemorrhage on MRI scan at a field strength of 3T [ Time Frame: Time zero equals baseline, up to 9 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 196
Study Start Date: December 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imaging Biomarkers Other: PET scan using florbetapir
A single intravenous microdose of 260 MBq (7 mCi) 18F-AV-45 (florbetapir F 18) will be administered.
Other Name: AV-45
Other: MRI Scan
Three different measurements will be taken: volumetric MRI (vMRI), diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI). In addition, radiological MRI scans will be taken to monitor vasogenic edema and microhemorrhages.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Present with prodromal Alzheimer's Disease (AD) or mild AD based on the disease diagnostic criteria
  • Are men or post-menopausal women, at least 55 years of age. Post-menopausal women are defined as women who have had a hysterectomy and/or bilateral oophorectomy; or who have been amenorrheic for at least 2 years
  • Have a caretaker/study informant who provides a separate written informed consent to participate. If a caretaker/study informant cannot continue, one replacement is allowed
  • Gradual and progressive change in memory function reported by participants or informants over more than 6 months
  • Objective evidence of significantly impaired episodic memory characteristic of hippocampal dysfunction on testing: Free and Cued Selective Reminding Test (FCSRT): less than or equal to 16 for free recall or less than or equal to 40 for total recall
  • Clinical Dementia Rating (CDR) equals 0.5 or 1, Memory box score greater than or equal to 0.5
  • Mini Mental Scale Examination (MMSE) 20-30
  • Positive florbetapir F 18 scan
  • Participants must meet all of the Disease Diagnostic Criteria to be considered for enrollment

Exclusion Criteria:

  • Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders
  • Frontotemporal dementia, Lewy body disease, vascular dementia, Huntington's Disease or concomitant Parkinson's disease, progressive supranuclear palsy (PSNP) or other movement disorder
  • Has B12 <200 pg/L or folate <7.5 nmol/L indicating vitamin deficiency
  • Has a history within the past 5 years of a serious infectious disease affecting the brain, including meningitis, or encephalitis
  • Significant history of alcoholism or substance abuse (at the judgment of the investigator)
  • Severe or recurrent head injury that is clinically relevant to the disease under study, (that is, with permanent neurological/cognitive sequelae)
  • Onset of dementia following heart surgery or cardiac arrest
  • Diagnosis or history of cerebrovascular disease (for example, stroke, transient ischemic attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's current cognitive or functional status, impair ability to fully participate in the trial or that may impact status
  • Has had a Positron Emission Tomography (PET) within 6 months of the scheduled imaging follow-up
  • Greater than 4 cerebral microhemorrhages (CMH) on T2* -weighted gradient-recalled echo sequences (regardless of their anatomical or diagnostic characterization as "possible" or "definite"), a single area of superficial siderosis, or prior evidence of macrohemorrhage
  • Any indications of severe deep white matter lesions or vasogenic edema that present as hyperintense regions on the Fluid Attenuated Inversion Recovery (FLAIR) sequence, or other clinically relevant findings observed on the Magnetic Resonance Imaging (MRI) scans
  • Specific exclusionary brain MRI findings, as determined by the investigator in consultation with the sponsor, that could either contribute to the patient's current cognitive or functional decline impair ability to fully participate in the trial or that may impact status during the trial (for example, brain tumors or other non-vascular structural abnormalities like hydrocephalus)
  • History within the past 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen (PSA) post resection
  • History of clinically significant cardiovascular or renal events
  • Diastolic blood pressure of 95 or more and systolic blood pressure of 160 or more in sitting position after at least 5 minutes of rest
  • Any history of seizure
  • History of clinically significant head trauma or clinically significant unexplained loss of consciousness within the last 5 years (as determined by the investigator in consultation with the Sponsor)
  • A current Axis I diagnosis of major depressive disorder or other psychiatric illness (Diagnostic and Statistical Manual Revised Fourth Edition [DSM-IV-TR]) criteria per the investigator's judgment. (Note: Patients on a stable antidepressant and/or anxiolytic treatment may participate.)
  • Having suicidal ideations, or attempted suicide in the past 15 years
  • History of schizophrenia, bipolar disorder, or other severe mental illness
  • Known history of alcohol or drug abuse (as defined by the DSM-IV-TR) within 5 years prior to enrolling or a positive result regarding use of illicit drugs on the drug screening test
  • Chronic hepatic diseases as indicated by liver function test abnormalities (alanine trasaminase [ALT], aspartate transaminase [AST], bilirubin, or gamma-glutamyl transferase [GGT] above 2 times upper limit of normal), positive serology for Hepatitis B or C, or other manifestations of liver disease
  • Has compromised renal function at screening, as determined by creatinine clearance <30 mL/min based on Cockcroft-Gault calculation of creatinine clearance
  • History of asthma, chronic obstructive pulmonary disease, or other chronic respiratory conditions
  • Known positive human immunodeficiency virus (HIV) status, history of syphilitic infection
  • A clinically significant abnormality in the 12-lead electrocardiograms (ECG), including complete heart block, bradycardia (heart rate <50 beats/minute), tachycardia (heart rate ≥95 beats/minute), sinus pauses >2 seconds, second or third degree heart block, QTc >450 msec for males or QTc >470 for females
  • Treatment with an investigational small molecule within 1 year preceding the first study period, or participation in a trial with active or passive immunization against amyloid if patient was assigned to the active treatment arm
  • Fulfillment of any contraindications to a 3T magnetic resonance imaging (MRI) scan (for example, subjects with non-removable ferromagnetic implants (such as cardiac pacemaker), aneurysm clips or other foreign bodies, or subjects with claustrophobic symptoms that would contraindicate an MRI scan)
  • Sensitivity to florbetapir F 18
  • Are not capable of swallowing whole oral medications
  • Abnormal thyroid function

    • Thyroid stimulating hormone (TSH) values are outside of the normal range 0.3-5.6 mIU/L. (NOTE: patients with stable treatment of hypothyroidism and with normal value of TSH will be allowed to enter the study)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459016

Locations
France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Cahors, France, 46005
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Castres, France, 81108
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Foix Cedex, France, 09017
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Lavaur, France, BP85 81502
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Lille, France, 59037
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Limoges, France, 87042
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Léon, France, 33076
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Marseille, France, 13385
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Montauban Cedex, France, 82013
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Nancy, France, 54511
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Paris, France, 75651
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Rennes, France, 35000
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Strasbourg, France, 67091
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Toulouse, France, 31059
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Tours, France, 37044
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Vic-En-Bigorre, France, 65500
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri, 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01459016     History of Changes
Other Study ID Numbers: 14162, I4O-MC-BACH
Study First Received: October 12, 2011
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Eli Lilly and Company:
Mild Cognitive Impairment
Brain Imaging Biomarkers
Magnetic resonance imaging biomarker
Positron Emission Tomography

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 29, 2014