Clinical trial NCT01388478: Safety Study of R(+)Pramipexole to Treat Early Alzheimer's Disease
Official title: Safety/Tolerability and Effects on Cognitive Impairment, Impaired Cerebral Cortical Metabolism and Oxidative Stress of R(+)Pramipexole Administered to Subjects With Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Safety
Tolerability
R(+)Pramipexole
Alzheimer's
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: University of Kansas
name: Alzheimer's Drug Discovery Foundation
First posted: 2011-07-06
Enrollment: 20
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: By doing this study, researchers will examine the safety and tolerability of R-pramipexole in participants with Alzheimer's disease. This study will also examine the body and brain's response to the study drug by measuring the amount of injury to the cells (oxidative stress) in the blood and spinal fluid and brain imaging before and after treatment.

Detailed description: Subjects will be recruited from the Univ of Kansas Alzheimer's Center and will provide informed consent about participating.

R(+)-pramipexole will be provided as Good Manufacturing Practice powder and taken as a liquid and start at one teaspoon (5 ml) twice a day for a total dose of 100 mg/day. After 4 weeks, the dose will double (two teaspoons twice a day, or a total of 200mg/day). Four weeks later the dose will be increased again to 2 1/2 teaspoons twice a day (total of 300mg/day) where it will remain for the remaining 16 weeks of study treatment. Prior to each increase, participants and their study partners will be interviewed regarding any possible side effects or problems. These findings will be discussed with Dr. Burns prior to increasing the study drug dose. The dose will only increase if the participant is not having side effects.

Primary Outcome Measure:

1.Number of Patients with Adverse Events \[Time Frame: Every 2 months\] \[Safety Issue: Yes\]

Labwork will be performed every two months. There will be frequent contact with subjects to assess for adverse events.

Secondary Outcome Measures:

Reduction of Oxidative Stress \[Time Frame: Baseline and at 24 weeks after taking study drug\] \[Safety Issue: No\]

A lumbar puncture (spinal tap) will be performed to collect cerebral spinal fluid, which will be assayed for isoprostane levels before and after treatment.

Changes in cerebral glucose metabolism \[Time Frame: Baseline and at 24 weeks after taking drug\] \[Safety Issue: No\]

Positron Emission Tomography Scan will be performed. Changes in cerebral glucose metabolism as a proxy for mitochondrial respiration will be assayed at baseline and 24 weeks. Correlations will be sought with assays of oxidative stress reduction to see if greater reductions in brain oxidative stress are reflected in elevations of cortical 2-fluorodeoxyglucose.

Effects on Cognitive Performance \[Time Frame: Baseline and then 6 months thereafter\] \[Safety Issue: Yes\]

Quantitative assessment of cognitive status will be taken at baseline and at end of 6 month dosing period.

Eligibility criteria: Inclusion Criteria:

* Informed consent provided by the participant or the participant's legally acceptable representative
* Age 55 years or older
* Possible/probable Alzheimer's Disease (AD)
* Community dwelling with a caregiver able and willing to accompany the participant on all visits, if necessary. Caregiver must visit with the subject \>5 times per week.
* Rosen Modified Hachinski score of 4 or less
* Imaging Study (CT or MRI) compatible with AD or age-related changes (absence of significant abnormalities that may explain cognitive decline, such as multiple lacunar infarcts or a single prior infarct \>1 cubic cm, microhemorrhages or evidence of a prior hemorrhage \> 1 cubic cm, evidence of cerebral contusion encephalomalacia, aneurysm, vascular malformation, or space occupying lesion such as an arachnoid cyst or brain tumor).
* Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments

Exclusion Criteria:

* Significant neurological disease, other than AD, that may affect cognition
* Current clinically-significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
* History of clinically-evident stroke
* Clinically-significant infection within the last 30 days
* Myocardial infarction or symptoms of active coronary artery disease (e.g., angina) in the last two years.
* Uncontrolled hypertension within the last 6 months.
* History of cancer within the last 5 years (except non-metastatic basal or squamous cell carcinoma)
* History of drug or alcohol abuse as defined by DSM-IV criteria within the last 2 years
* Insulin dependent diabetes mellitus
* Significant pain or musculoskeletal disorder that would prohibit participation in metabolic testing

Primary outcomes:
measure: Number of Patients With Adverse Events
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
measure: Effects on Cognitive Performance
timeFrame: Baseline and then 6 months thereafter
measure: Changes in Cerebral Glucose Metabolism
timeFrame: Baseline and at 24 weeks after taking drug
measure: Reduction of Oxidative Stress
timeFrame: Baseline and at 24 weeks after taking study drug
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: Virginia Commonwealth University
name: James P. Bennett, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kansas
name: Jeffrey M Burns, MD
role: PRINCIPAL_INVESTIGATOR
References: