Alzheimer Disease
Conditions
Keywords
Salsalate
Brief summary
The purpose of the study is to test the safety and tolerability of twice daily Salsalate in patients with mild to moderate Alzheimer's Disease. Half of the participants will receive Salsalate and half will receive placebo during the 1-year duration of the study.
Detailed description
This is a Phase 1b, 12-month, randomized, double-blind, placebo-controlled study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of salsalate in patients with mild to moderate AD. Approximately 40 subjects will be randomized 1:1 to placebo or active. All study drugs will be administered orally bid \[two placebo tablets bid or two 750 mg salsalate tablets bid (for a total daily dose of 3,000 mg)\] for 12 months. This study will test the effects of Salsalate on cerebrospinal fluid (CSF) proteins, brain magnetic resonance imaging (MRI), and cognitive (thinking and memory) tests in subjects with mild to moderate AD. This study uses placebo which looks like the experimental drug but does not have any active drug in it.
Interventions
DRUGSalsalate
Salsalate is a non-acetylated dimer of salicylic acid, and is classified as a non-steroidal anti-inflammatory drug (NSAID). Salsalate has been commercially available in the US as a prescription drug for the relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and related rheumatic disorder for decades.
DRUGPlacebo
Inactive ingredient
Sponsors
Adam Boxer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-Blind study. Only investigational pharmacist will be unblinded.
Intervention model description
Randomized, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Between 50 and 85 years of age (inclusive); 2. Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD dementia (McKhann et al. 2011) (30); 3. MRI at Screening is consistent with AD (≤ 4 microhemorrhages, and no large strokes or severe white matter disease); 4. MHIS at Screening is ≤ 4; 5. MMSE at Screening is between 14 and 30 (inclusive); 6. FDA-approved AD medications are allowed as long as the dose is stable for 2 months prior to initial Screening visit. Other medications (except those listed under
Exclusion criteria
) are allowed as long as the dose is stable for 30 days prior to initial Screening visit; 7. Has a reliable study partner who agrees to accompany the subject to visits, and spends at least 5 hours per week with the subject; 8. Agrees to the lumbar puncture and CSF collection at Screening and after 11.5 months of study drug administration. The lumbar puncture and CSF collection at the end of Month 6 is optional and is not required for eligibility; 9. Positive amyloid PET scan at Screening. Previous amyloid PET scan positivity or previous AD biomarker (Aβ/tau level) positivity may be used instead of performing an amyloid PET scan at Screening at the Investigator's discretion; 10. Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations; 11. Males and all WCBP agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 12 months | Assess adverse events during 12 months administration of Salsalate or Placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pharmacokinetic properties of Salsalate in Plasma and Cerebrospinal Fluid | 6; 11.5 months | Measure steady-state plasma and cerebrosinal fluid concentrations of salsalate and its metabolites. |
| Changes in Pharmacodynamic properties of Salsalate in Cerebrospinal Fluid | 6; 11.5 months | Measure CSF concentrations of total tau, phosphorylated tau, and neurofilament light chain |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Cerebrospinal Fluid Biomarkers of neurofilament light chain | 6; 11.5 months | Measure CSF concentrations of neurofilament light chain protein (NfL) pg/ml |
| Change in Cerebrospinal Fluid Biomarkers of total tau | 6; 11.5 months | Measure CSF concentrations of total tau protein (t-tau) pg/mL |
| Change in Cerebrospinal Fluid Biomarkers of beta amyloid 1-42 | 6; 11.5 months | Measure CSF concentrations of beta amyloid protein (Abeta1-42) pg/mL |
| Change in brain volume on brain MRI | 6; 12 months | Measure of global and regional volumes of interest (such as hippocampus) |
| Change in Mini Mental State Examination | 6;12 months | Measure changes using the Mini Mental State Exam (MMSE) which evaluates cognitive function. |
| Change in Alzheimer's disease Clinical Activities of Daily Living Scale | 6;12 months | Measure changes in function, and in particular the degree of disability using the Alzheimer's disease Clinical Activities of Daily Living scale (ADCS-ADL) |
| Change in Clinical Dementia Rating Scale (CDR-SB) | 6;12 months | Measure change in dementia status using the Clinical Dementia Rating scale (CDR-SB) |
| Change in Alzheimer's Disease Assessment Scale-cognitive scale | 6;12 months | Measure changes using the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) which evaluates cognitive dysfunctions |
| Change in structural and functional connectivity on brain MRI | 6; 12 months | Connectivity between brain regions measured using diffusion tensor MRI and resting state functional MRI |
| Change in Cerebrospinal Fluid Biomarkers of phosphorylated tau | 6; 11.5 months | Measure CSF concentrations of phosphorylated tau protein (p-tau) pg/mL |
Countries
United States
Outcome results
None listed