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

Lilly

Status and phase

Completed

Phase 1

Conditions

Alzheimer's Disease

Treatments

Other: MRI Scan

Other: PET scan using florbetapir

Study type

Interventional

Funder types

Industry

Identifiers

NCT01459016

I4O-MC-BACH (Other Identifier)

14162

Details and patient eligibility

About

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.

Full description

After trial initiation, the protocol was amended to extend the single observation time period (6 to 9 months) to two time points (6 and 12 months), and to focus on prodromal AD (Mini-Mental State Examination [MMSE] 23-30 inclusive, Free and Cued Selective Reminding Test [FCSRT] less than or equal to [≤] 24 for free recall or ≤ 44 for total recall). Participants enrolled under the original protocol were allowed to continue in the extension study if they so desired, and if they met the new inclusion criteria. Due to the number of participants that completed the extended trial, no sub-group analysis was performed based on which amendment the participants entered under.

Enrollment

56 patients

Sex

All

Ages

55+ years old

Volunteers

No Healthy Volunteers

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 ≤ 40 for total recall. Protocol amendment: FCSRT ≤ 24 for free recall or ≤ 44 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. Protocol amendment: MMSE 23-30, inclusive
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 participant'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: Participants 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 participant 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: Participants with stable treatment of hypothyroidism and with normal value of TSH will be allowed to enter the study)