Clinical trial NCT00105105: Mifepristone as Adjunctive Therapy in Alzheimer's Disease
Official title: A Double-blind, Placebo-controlled Trial of the Safety and Efficacy of C-1073 (Mifepristone) as Adjunctive Therapy in Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimers
cognition
acetyl cholinesterase inhibitor
GR-II antagonist
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
Collaborators: name: Institute for the Study of Aging (ISOA)
First posted: 2005-03-07
Enrollment: 160
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effects of C-1073 (Mifepristone) on cognition in patients with Alzheimer's disease (AD) who are also taking an acetylcholinesterase inhibitor (Aricept, Exelon or Reminyl).

Detailed description: This will be a double blind, placebo controlled study of C-1073 to evaluate the effects on cognition in patients with mild to moderate Alzheimer's disease who are already receiving an acetylcholinesterase inhibitor and have been on a stable dose for at least 12 weeks. Patients will be randomized (1:1) to either daily dosing with 300 mg C-1073 or a placebo for 16 weeks. Patients will continue the stable daily dose of acetylcholinesterase inhibitor throughout the study.

Visits will be weekly at the beginning of the study, then every two weeks, and every 4 weeks after week 12. Assessments during these visits may include cognition and behavior, depression, safety, as well as physical exams, clinical laboratory tests, EKG and adverse event reporting.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Alzheimer's disease
* Women must have had a partial or complete hysterectomy
* Mini Mental Status Evaluation score of 18-27
* HAM-D score less than or equal to 18
* Able to provide written informed consent
* On a stable dose of an acetylcholinesterase inhibitor for at least 12 weeks prior to screening visit
* Ambulatory, or ambulatory with walker or cane
* Sufficient hearing and vision to enable the patient to comply with the study procedures
* Caregiver available to participate in the assessment of the patient and monitor dosing

Exclusion Criteria:

* Women with an intact uterus
* A clinically significant medical condition, including lab abnormality, which in the opinion of the investigator would place the patient at undue risk, or would impair the patient's ability to participate in the study. These include but are not limited to: history of cerebral vascular accident (CVA), adrenal insufficiency, porphyrias, autoimmune disorders, type I diabetes, chronic obstructive pulmonary disease (COPD), hematologic or oncologic disorders in the previous 2 years, vitamin B12 or folate deficiency
* A clinically significant active gastrointestinal, renal, hepatic, endocrine, or cardiovascular system disease that is not well controlled by diet, pharmacological treatment, or other therapeutic intervention
* History of psychotic episodes or bipolar disorder, or additional diagnosis of delusions, delerium, or depression
* Evidence of other psychiatric or neurologic disorders (e.g., stroke, schizophrenia, or Parkinson disease)
* Hachinski ischemia score of 5 or more
* Known hypersensitivity to cholinesterase inhibitors
* Use of systemic or pulmonary inhaled corticosteroids within the 30 days prior to randomization, or require use of these medications during the study
* Use of memantine (Namenda) within the 30 days prior to randomization, or require use of this medication during the study
* Currently taking medications known to significantly induce or inhibit the metabolism of CYP 3A4, or have taken these medications 7 days prior to randomization (see list below under prohibited medications)
* Use of anticholinergic compounds within the 30 days prior to randomization, or require use of this medication during the study
* History of electroconvulsive therapy (ECT); patients may not undergo ECT during the course of the trial
* Positive urine drug screen for any non-prescribed drug of abuse (including but not limited to amphetamines, cannabinoids, barbiturates, cocaine, opiates, benzodiazepines)
* History of illicit drugs usage or a history of drug or alcohol dependence
* Known to have another form of dementia that may also explain the patient's deficits including reversible dementias, Binswanger's, Parkinson's dementia complex, Korsakoff's, mental retardation or vascular dementia. Patients who meet clinical criteria for AD but who have deep white matter lesions on MRI or CT scan will be accepted.
* Currently taking prescription anticoagulants such as warfarin (Coumadin)
* Planned surgical procedures during the study period, including the 4 week off drug period between weeks 16 and 20
* Participation in a clinical investigation of any drug, or other biological or investigational therapy within 30 days prior to dosing
* Previous participation in a trial using mifepristone, or known sensitivity or allergy to C-1073 (mifepristone) or its constituents
* Body Mass Index (BMI) over 35

Prohibited Medications:

Medications known to significantly induce or inhibit the metabolism of CYP 3A4, specifically:

* carbamazepine (Carbatrol® Tegretol®)
* modafinil (Provigil®)
* nefazodone (Serzone®)
* droperidol
* erythromycin
* fluconazole (Diflucan®)
* itraconazole (Sporanox®)
* ketoconazole (Nizoral®)
* simvastatin (Zocor®)
* lovastatin (Mevacor®)
* vinblastine
* vincristine
* paclitaxel (Taxol®)
* tamoxifen (Nolvadex®)
* cyclosporine (Neoral®, Sandimmune®)
* tacrolimus (Gengraf®)
* sirolimus (Rapamune®)
* midazolam (Versed®)
* nicardipine (Cardene®)
* nifedipine (Adalat®, Procardia®)
* felodipine (Lexxel®, Plendil®)
* thioridizine
* pimozide (Orap®)
* quinidine
* Patient may also not take St. John's Wort during the study or within 7 days prior to study entry
* the use of grapefruit juice will be excluded during the course of the study.
* use of anticholinergic compounds over the past 30 days prior to randomization
* warfarin (Coumadin)
* all systemic and inhaled pulmonary corticosteroids
* memantine (Namenda)

Primary outcomes:
measure: effects on cognition
Secondary outcomes:
measure: effects on behavior and activities of daily living
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Pivotal Research Center
state: Arizona
city: Peoria
country: United States
facility: Pivotal Research Center
state: Arizona
city: Fountain Valley
country: United States
facility: ATP Clinical Trials
state: California
city: Orange
country: United States
facility: UCI Irvine Medical Center
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: Torrance
country: United States
facility: AVI Clinical Research
state: California
city: Boca Raton
country: United States
facility: Baumel-Eisner Neuromed Inst
state: Florida
city: Ft. Lauderdale
country: United States
facility: Baumel-Eisner Neuromed Inst
state: Florida
city: Ft. Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Miami Beach
country: United States
facility: Baumel-Eisner Neuromed Inst
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Tampa
country: United States
facility: Johnnie B. Byrd, Sr. Alzheimer's Center & Research Inst
state: Florida
city: Long Branch
country: United States
facility: Memory Enhancement Center
state: New Jersey
city: New York
country: United States
facility: Eastside Medical Research
state: New York
city: Toledo
country: United States
facility: Neuro Center of Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: Pahl Pharmaceutical Research, LLC
state: Oklahoma
city: Tulsa
country: United States
facility: Clinical Pharmaceutical Trials, Inc.
state: Oklahoma
city: Pittsburgh
country: United States
facility: Clinical Trials Research Services
state: Pennsylvania
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: Richmond
country: United States
facility: International Clinical Research Associates
state: Virginia
city: Virginia Beach
country: United States
facility: International Clinical Research Associates
state: Virginia
Study officials:
References:
citation: Belanoff JK, Jurik J, Schatzberg LD, DeBattista C, Schatzberg AF. Slowing the progression of cognitive decline in Alzheimer's disease using mifepristone. J Mol Neurosci. 2002 Aug-Oct;19(1-2):201-6. doi: 10.1007/s12031-002-0033-3.