Salsalate in Patients Mild to Moderate Alzheimer's Disease

NCT03277573 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: UC-SAL-AD-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Alzheimer Disease

Keywords

Salsalate

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Assess adverse events during 12 months administration of Salsalate or Placebo

  12 months

Secondary Outcomes (2)

• Changes in Pharmacokinetic properties of Salsalate in Plasma and Cerebrospinal Fluid

  6; 11.5 months

• Changes in Pharmacodynamic properties of Salsalate in Cerebrospinal Fluid

  6; 11.5 months

Other Outcomes (10)

• Change in brain volume on brain MRI

  6; 12 months

• Change in structural and functional connectivity on brain MRI

  6; 12 months

• Change in Cerebrospinal Fluid Biomarkers of phosphorylated tau

  6; 11.5 months

Study Arms (2)

Salsalate

EXPERIMENTAL

Drug: Salsalate 2 tablets twice daily (3,000 mg total daily) by mouth for 12 months

Drug: Salsalate

Placebo

PLACEBO COMPARATOR

Drug: Placebo 2 tablets twice daily by mouth for 12 months

Drug: Placebo

Interventions

Salsalate DRUG

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.

Salsalate

Placebo DRUG

Inactive ingredient

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 50 and 85 years of age (inclusive);
• Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD dementia (McKhann et al. 2011) (30);
• MRI at Screening is consistent with AD (≤ 4 microhemorrhages, and no large strokes or severe white matter disease);
• MHIS at Screening is ≤ 4;
• MMSE at Screening is between 14 and 30 (inclusive);

You may not qualify if:

• Has a reliable study partner who agrees to accompany the subject to visits, and spends at least 5 hours per week with the subject;
• 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;
• 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;
• Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations;
• 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.
• Any medical condition other than AD that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);
• History of negative AD biomarker studies (CSF Aβ/tau levels or amyloid PET), or a negative amyloid PET scan during Screening;
• History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
• Systolic blood pressure exceeding 180 mmHg or diastolic blood pressure exceeding 100 mmHg at Screening or Baseline;
• History of peptic ulcer disease or GI bleeding;
• History of asthma, urticaria, or allergic-type reactions after taking NSAIDs or aspirin;
• History of aspirin triad (i.e., aspirin allergy, nasal polyps, and asthma);
• History of autoimmune disorders deemed clinically significant by the Investigator;
• History of major psychiatric illness or major depression that in the opinion of the Investigator would pose a safety risk or interfere with the appropriate interpretation of study data;
• Neutrophil count \<1,500/mm3, platelets \<100,000/mm3, serum creatinine \>1.5 x upper limit of normal (ULN), total bilirubin \>1.5 x ULN, alanine aminotransferase (ALT) \>3 x ULN, aspartate aminotransferase (AST) \>3 x ULN, or INR \>1.2 at Screening;

Sponsors & Collaborators

• Adam Boxer: lead

Study Sites (2)

University of California, San Diego

San Diego, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (9)

• Min SW, Chen X, Tracy TE, Li Y, Zhou Y, Wang C, Shirakawa K, Minami SS, Defensor E, Mok SA, Sohn PD, Schilling B, Cong X, Ellerby L, Gibson BW, Johnson J, Krogan N, Shamloo M, Gestwicki J, Masliah E, Verdin E, Gan L. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat Med. 2015 Oct;21(10):1154-62. doi: 10.1038/nm.3951. Epub 2015 Sep 21.

  PMID: 26390242 BACKGROUND

• Montine TJ, Larson EB. Late-life dementias: does this unyielding global challenge require a broader view? JAMA. 2009 Dec 16;302(23):2593-4. doi: 10.1001/jama.2009.1863. No abstract available.

  PMID: 20009062 BACKGROUND

• Jack CR Jr, Holtzman DM. Biomarker modeling of Alzheimer's disease. Neuron. 2013 Dec 18;80(6):1347-58. doi: 10.1016/j.neuron.2013.12.003.

  PMID: 24360540 BACKGROUND

• Green RC, Schneider LS, Amato DA, Beelen AP, Wilcock G, Swabb EA, Zavitz KH; Tarenflurbil Phase 3 Study Group. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA. 2009 Dec 16;302(23):2557-64. doi: 10.1001/jama.2009.1866.

  PMID: 20009055 BACKGROUND

• Gauthier S, Aisen PS, Ferris SH, Saumier D, Duong A, Haine D, Garceau D, Suhy J, Oh J, Lau W, Sampalis J. Effect of tramiprosate in patients with mild-to-moderate Alzheimer's disease: exploratory analyses of the MRI sub-group of the Alphase study. J Nutr Health Aging. 2009 Jun;13(6):550-7. doi: 10.1007/s12603-009-0106-x.

  PMID: 19536424 BACKGROUND

• Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA. Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet. 2008 Jul 19;372(9634):216-23. doi: 10.1016/S0140-6736(08)61075-2.

  PMID: 18640458 BACKGROUND

• Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, Siemers E, Liu-Seifert H, Mohs R; Alzheimer's Disease Cooperative Study Steering Committee; Solanezumab Study Group. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):311-21. doi: 10.1056/NEJMoa1312889.

  PMID: 24450890 BACKGROUND

• Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR; Bapineuzumab 301 and 302 Clinical Trial Investigators. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):322-33. doi: 10.1056/NEJMoa1304839.

  PMID: 24450891 BACKGROUND

• Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA, Martinez A, Santos A, Perez-Castillo A. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. J Neurosci. 2007 May 23;27(21):5766-76. doi: 10.1523/JNEUROSCI.1004-07.2007.

  PMID: 17522320 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Adam Boxer, MD, PhD

  UCSF Memory and Aging Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind study. Only investigational pharmacist will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Alzheimer's Disease and Frontotemporal Dementia Clinical Trials Program, Professor of Neurology

Model Details: Randomized, Double-Blind, Placebo-Controlled

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: September 11, 2017
• Study Start: July 21, 2017
• Primary Completion: February 4, 2022
• Study Completion: April 10, 2023
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)