A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy

NCT02422485 | Completed Phase 1 FDA Drug

• 1 other identifier: Salsalate PSP
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-center, open label, pilot futility clinical trial of the safety, tolerability, pharmacodynamics and preliminary efficacy of oral salsalate in up to 10 patients with PSP.

Conditions

Progressive Supranuclear Palsy

Keywords

Salsalate

Outcome Measures

Primary Outcomes (1)

• Number of patients experiencing drug limiting toxicity (DLT),

  defined as: 1) any Grade 3 or higher adverse event (AE) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) for which there is reasonable possibility that salsalate caused the event, 2) any Grade 2 AE in the CTCAE system organ class of nervous system disorders that is considered clinically significant and for which there is reasonable possibility that salsalate caused the event, or 3) any Grade 2 or higher treatment-related adverse events during administration that do not resolve promptly with supportive treatment.

  6 months

Secondary Outcomes (4)

• Changes in motor function

  6 months

• Changes in cognition

  6 months

• Changes in activities of daily living

  6 months

• Changes in behavior

  6 months

Other Outcomes (5)

• Changes in concentration of cerebrospinal fluid (CSF) biomarkers

  6 months

• Changes in brain volume

  6 months

• Changes in motor function, cognition, activities of daily living, and behavior

  6 months

Study Arms (1)

Salsalate

EXPERIMENTAL

All participants will be administered 2,250 mg daily \[1,500 mg every day before noon (every AM) and 750 mg every night at bedtime (every HS)\] for 6 months.

Drug: Salsalate

Interventions

Salsalate DRUG

Salsalate is a non-acetylated dimer of salicylic acid, and is classified as a NSAID. The chemical name of salsalate is 2-hydroxy-benzoic acid, 2-carboxyphenyl ester. Salsalate has a molecular weight (MW) of 258.226 Da and a molecular formula of C14H10O5.

Salsalate

Eligibility Criteria

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

You may qualify if:

• Meets National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria,(Litvan 1996a) as modified from the AL-108-231 trial.(Boxer 2014)
• Aged 50-85
• Agrees to 3 magnetic resonance imaging (MRI) or subject to investigator's discretion
• MRI at screening is consistent with PSP (≤4 microhemorrhages and no large strokes or severe white matter disease)
• Mini-Mental State Examination (MMSE) score 14-30
• Stable medications for 2 months prior to screening, including FDA approved Alzheimer's disease (AD) medications and Parkinson's disease medications
• Availability of a study partner who knows the patient well and is willing to accompany the patient to all trial visits and to participate in questionnaires
• Agrees to 2 lumbar punctures for cerebrospinal fluid (CSF) examination
• Signed and dated written informed consent obtained from the subject and 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.
• Adequate contraceptive methods include those with a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as complete abstinence from sexual intercourse with a potentially fertile partner, and some double barrier methods condom with spermicide) in conjunction with use by the partner of an intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, birth control patch or vaginal ring, oral, or injectable or implanted contraceptives.
• For this study, a woman who has been surgically sterilized or who has been in a state of amenorrhea for more than two years will be deemed not to be of childbearing potential;

You may not qualify if:

• Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD (McKhann et al. 2011);
• Any medical condition other than PSP that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);
• A prominent and sustained response to levodopa therapy;
• History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
• History of hypertension (repeated elevations in blood pressure exceeding 180 mm Hg systolic or 100 mm Hg diastolic; medical intervention indicated);
• History of severe gastrointestinal bleed, or gastric or peptic ulcers;
• History of aspirin triad (i.e., aspirin allergy, nasal polyps and asthma) or asthma;
• History of major psychiatric illness or untreated depression;
• 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 evaluations;
• Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data;
• Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
• Current clinically significant viral infection. Subjects with chicken pox, influenza, or flu symptoms are not eligible;
• Major surgery within four weeks prior to Screening;
• Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening;
• Treatment with another investigational drug or participation in another interventional clinical trial within 3 months of Screening;

Sponsors & Collaborators

• Adam Boxer: lead

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

OHSU Parkinson Center & Movement Disorder Program

Portland, Oregon, 97239, United States

Location

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MeSH Terms

Conditions

Supranuclear Palsy, Progressive

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Adam Boxer, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 9, 2015
• First Posted: April 21, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 1, 2021

Record last verified: 2021-03

Locations

US (2)