Alzheimer's Disease
Conditions
Keywords
Safety, Tolerability, R(+)Pramipexole, Alzheimer's
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.
Interventions
DRUGR-pramipexole
R-pramipexole will be 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 the physician prior to increasing the study drug dose. The dose will only increase if the participant is not having side effects.
Sponsors
University of Kansas
Alzheimer's Drug Discovery Foundation
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events | 6 months | Labwork will be performed every two months. There will be frequent contact with subjects to assess for adverse events. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Effects on Cognitive Performance | Baseline and then 6 months thereafter | Quantitative assessment of cognitive status will be taken at baseline and at end of 6 month dosing period. |
| Changes in Cerebral Glucose Metabolism | Baseline and at 24 weeks after taking drug | PET 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-FDG. |
| Reduction of Oxidative Stress | Baseline and at 24 weeks after taking study drug | A lumbar puncture (spinal tap) will be performed to collect cerebral spinal fluid, which will be assayed for isoprostane levels before and after treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| R(+)Pramipexole Each study participant will be given the active study drug, R-pramipexole. There is no placebo arm.
R-pramipexole: R-pramipexole will be 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 the physician prior to increasing the study drug dose. The dose will only increase if the participant is not having side effects. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | R(+)Pramipexole | — |
|---|---|---|
| Age, Continuous | 70.2 years STANDARD_DEVIATION 7.9 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 20 participants | — |
| Sex: Female, Male Female | 8 Participants | — |
| Sex: Female, Male Male | 12 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 18 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Number of Patients With Adverse Events
Labwork will be performed every two months. There will be frequent contact with subjects to assess for adverse events.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| R(+)Pramipexole | Number of Patients With Adverse Events | 18 Participants |
Other Pre-specified
Changes in Cerebral Glucose Metabolism
PET 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-FDG.
Time frame: Baseline and at 24 weeks after taking drug
Other Pre-specified
Effects on Cognitive Performance
Quantitative assessment of cognitive status will be taken at baseline and at end of 6 month dosing period.
Time frame: Baseline and then 6 months thereafter
Other Pre-specified
Reduction of Oxidative Stress
A lumbar puncture (spinal tap) will be performed to collect cerebral spinal fluid, which will be assayed for isoprostane levels before and after treatment.
Time frame: Baseline and at 24 weeks after taking study drug