This trial is active, not recruiting.

Condition alzheimer's disease
Treatments pet scan using florbetapir, mri scan
Phase phase 1
Sponsor Eli Lilly and Company
Start date December 2011
End date January 2015
Trial size 196 participants
Trial identifier NCT01459016, 14162, I4O-MC-BACH


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose basic science
pet scan using florbetapir AV-45
A single intravenous microdose of 260 MBq (7 mCi) 18F-AV-45 (florbetapir F 18) will be administered.
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.

Primary Outcomes

Change from baseline up to 9 months in volumetric magnetic resonance imaging (vMRI)
time frame: Time zero equals baseline, up to 9 months
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
Change from baseline up to 9 months in diffusion tensor imaging (DTI)
time frame: Time zero equals baseline, up to 9 months

Secondary Outcomes

Baseline brain amyloid load using Positron Emission Tomography (PET) and florbetapir
time frame: Time zero equals baseline
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
Number of participants with microhemorrhage on MRI scan at a field strength of 3T
time frame: Time zero equals baseline, up to 9 months

Eligibility Criteria

Male or female participants at least 55 years old.

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)

Additional Information

Official title An Exploratory Study of Brain Imaging Biomarkers in Patients With Alzheimer's Pathology Receiving Standard of Care
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.