Safety Study of R(+)Pramipexole to Treat Early Alzheimer's Disease

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01388478
• Other study ID #: VCU-KU-ADDF-2011
• Secondary ID: 20101202
• Status: Completed
• Phase: Phase 2
• Start date: July 2011
• Est. completion date: April 2014

Study information

• Verified date: September 2021
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Alzheimer's Drug Discovery Foundation, University of Kansas

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effects on Cognitive Performance	Quantitative assessment of cognitive status will be taken at baseline and at end of 6 month dosing period.	Baseline and then 6 months thereafter
Other	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.	Baseline and at 24 weeks after taking drug
Other	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.	Baseline and at 24 weeks after taking study drug
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.	6 months