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

March 30, 2021 updated by: Adam Boxer
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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. 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.

If ≥3 patients experience drug limiting toxicity (DLT), as defined below, the study will be terminated.

A DLT is 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.

An interim futility analysis will be performed after five subjects have completed 6 months of study drug treatment. If the criteria listed in the Statistical Methods section of this synopsis are met, an additional 5 subjects will be enrolled in the trial. If not, the trial will be terminated.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
    • Oregon
      • Portland, Oregon, United States, 97239
        • OHSU Parkinson Center & Movement Disorder Program

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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)
  2. Aged 50-85
  3. Agrees to 3 magnetic resonance imaging (MRI) or subject to investigator's discretion
  4. MRI at screening is consistent with PSP (≤4 microhemorrhages and no large strokes or severe white matter disease)
  5. Mini-Mental State Examination (MMSE) score 14-30
  6. Stable medications for 2 months prior to screening, including FDA approved Alzheimer's disease (AD) medications and Parkinson's disease medications
  7. 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
  8. Agrees to 2 lumbar punctures for cerebrospinal fluid (CSF) examination
  9. Signed and dated written informed consent obtained from the subject and subject's caregiver in accordance with local IRB regulations

  10. 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;

Exclusion Criteria:

  1. Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD (McKhann et al. 2011);
  2. Any medical condition other than PSP that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);
  3. A prominent and sustained response to levodopa therapy;
  4. History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
  5. History of hypertension (repeated elevations in blood pressure exceeding 180 mm Hg systolic or 100 mm Hg diastolic; medical intervention indicated);
  6. History of severe gastrointestinal bleed, or gastric or peptic ulcers;
  7. History of aspirin triad (i.e., aspirin allergy, nasal polyps and asthma) or asthma;
  8. History of major psychiatric illness or untreated depression;
  9. 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;
  10. 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;
  11. Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
  12. Current clinically significant viral infection. Subjects with chicken pox, influenza, or flu symptoms are not eligible;
  13. Major surgery within four weeks prior to Screening;
  14. 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;
  15. Treatment with another investigational drug or participation in another interventional clinical trial within 3 months of Screening;
  16. Chronic use of other NSAIDs or salicylates for any reason, except for daily baby aspirin (81 mg);
  17. Concurrent treatment with thiazides or loop diuretics;
  18. Concurrent use of oral corticosteroids or angiotensin-converting enzyme (ACE) inhibitors;
  19. Treatment with any human blood product, including intravenous immunoglobulin, during the 6 months prior to Screening or during the trial;
  20. Known hypersensitivity to the inactive ingredients in the study drug;
  21. Pregnant or lactating;
  22. Positive pregnancy test at Screening or Baseline (Day 1);
  23. Cancer within 5 years of Screening, except for non-metastatic skin cancer or nonmetastatic prostate cancer not expected to cause significant morbidity or mortality within one year of Baseline.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Salsalate
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients experiencing drug limiting toxicity (DLT),
Time Frame: 6 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in motor function
Time Frame: 6 months
Motor function as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months
Changes in cognition
Time Frame: 6 months
Cognitive function as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months
Changes in activities of daily living
Time Frame: 6 months
Activities of daily living as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months
Changes in behavior
Time Frame: 6 months
Behavior as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in concentration of cerebrospinal fluid (CSF) biomarkers
Time Frame: 6 months
Changes in the concentrations of cerebrospinal fluid (CSF) biomarkers
6 months
Changes in brain volume
Time Frame: 6 months
Changes in brain volume [T1-weighted volumetric magnetic resonance imaging (vMRI)], brain network functional and structural connectivity and perfusion [resting state functional magnetic resonance imaging (rsfMRI), diffusion tensor imaging (DTI), and arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI)]
6 months
Changes in motor function, cognition, activities of daily living, and behavior
Time Frame: 6 months
Motor function, cognition, activities of daily living, and behavior as measured by Schwab and England Activities of Daily Living scale (SEADL), PSP-Quality of Life. Scores range from one hundred percent, which indicates a completely independent individual, and zero percent, which indicates an individual in who is no longer functioning.
6 months
Changes in saccade eye movements
Time Frame: 6 months
To explore the effects of 2,250 mg daily salsalate on changes in saccade latency, velocity, and amplitude [infrared oculometry] from Screening to end of month 3 and end of month 6 compared to historical data;
6 months
Changes in sleep and activity levels
Time Frame: 6 months
Changes in actigraphic measures
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Adam Boxer

Investigators

  • Principal Investigator: Adam Boxer, MD, PhD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Actual)

December 1, 2019

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

April 9, 2015

First Submitted That Met QC Criteria

April 20, 2015

First Posted (Estimate)

April 21, 2015

Study Record Updates

Last Update Posted (Actual)

April 1, 2021

Last Update Submitted That Met QC Criteria

March 30, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Salsalate PSP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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