Nicotinic Acid for the treatment of Alzheimer's Disease Protocol Type: Interventional
Study on Investigational Medication for Alzheimer's Disease Treatment
Jared Brosch, MD
Primary Investigator
Brief description of study
The primary objective of this study is to collect data on the penetration of commercially available, FDA approved, extended-release niacin into the spinal fluid. One dose of 500 mg nicotinic acid will be used (in addition to placebo) to build a dose response curve for this compound in human cerebrospinal fluid. This objective will demonstrate target engagement of HCAR2 in the CNS after oral treatment with niacin. The primary endpoints are to show increased nicotinic acid levels in blood and CSF.
Detailed description of study
Participants will receive study drug (placebo or 500mg extended-release nicotinic acid).
- Study procedures include phlebotomy which will be performed by the study coordinator in the fasting state.
- Study cognitive, functional, and neuropsychiatric survey’s will be conducted in a closed room with minimal interruption.
- Lumbar punctures will be performed using 22 gauge sprotte style needles using gravity to collect 20ml +/- 2mL at the randomization visit and at the final visit. Participants will lie down for 60 minutes +/- 15 minutes after the procedure.
- Approximately 2 mL will be sent to the local laboratory for cell counts, protein, and glucose levels. Efforts will be made to collect CSF with the participant in a fasted state.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Alzheimer's Disease
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Age: 60 years - 85 years
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Gender: All
- o Age 60-85 males or females
o Clinically have a diagnosis of Alzheimer’s disease in the mild-moderate dementia range
o Mini Mental Status Examination (MMSE) between 14-24 inclusive
o Must be on a stable dose (30 days minimum) of a cholinesterase inhibitor and/or memantine (or absence thereof)
o Have a reliable co-participant who has at least 3 days of face-to-face contact per week with the patient and ensures medical compliance with the study drug.
o Neuroimaging (MRI or CT scan of the brain) should be available within 1 year of screening
- o Any contraindication to clinical lumbar puncture including increased intracranial pressure, posterior fossa mass, bleeding diathesis, use of antiplatelet medications other than aspirin, use of any anticoagulant
o Severe cerebrovascular disease
o History of large territory stroke
o Allergy or sensitivity to B-vitamins or nicotinic acid
o History of elevated liver function tests (ALT/AST > 2x the upper limit of normal) or known liver disease
o Current consumption of Vitamin B3 (any form, including nicotinic acid) – including multivitamins and energy drinks. Participants taking a supplement containing Niacin must washout for 4 weeks prior to screening to participate.
o Renal impairment of Stage 2 or greater
o Active, uncontrolled peptic ulcer disease
o Prior history of myocardial infarction or QTcF >460ms
o Cancer diagnosis within prior 5 years or cancer not in remission other than non-melanoma skin cancer
o Regular use of benzodiazepines
o Unstable dose of antipsychotic medications. Antipsychotic medications may be used if on a stable dose (30 days minimum) and will not interfere with study assessments in the opinion of the investigator. PI will document review and approval of medications used by participant concurrently with study participation. Changes in dosing of antipsychotic medication must be approved by the investigator for continued participation.
o Other medical diagnosis that could be contributory at the discretion of the primary investigator
This study investigates the use of an investigational medication for treating Alzheimer's disease, a condition that affects memory and thinking. The purpose of this study is to collect data on how well the investigational medication, which is a form of vitamin B3, reaches the spinal fluid. This will help understand if the medication can affect the brain in people with Alzheimer's disease.
Participants will receive either a placebo or the investigational medication. The study involves several procedures. Blood samples will be taken by the study coordinator while participants are fasting. Cognitive and memory tests will be conducted in a quiet room. A lumbar puncture, a procedure to collect spinal fluid, will be performed at the start and end of the study. Participants will rest after this procedure.
- Who can participate: Adults aged 60 to 85 with mild to moderate Alzheimer's disease can join. They must have a Mini Mental Status Examination score between 14 and 24 and be on a stable dose of certain Alzheimer's medications. A reliable co-participant is needed to assist with medical compliance. Neuroimaging is required, and exclusion criteria include severe medical conditions and recent participation in other clinical trials.
- Study details: Participants will take part in activities such as blood sampling and memory tests. They will receive either the investigational medication or a placebo, which is an inactive substance that looks like the investigational medication but does not contain any medicine. Blood samples will be taken while participants are fasting. A lumbar puncture will be conducted to collect spinal fluid at the start and end of the study.
