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

This study is currently recruiting participants.
Verified July 2017 by Adam Boxer, University of California, San Francisco
Sponsor:
ClinicalTrials.gov Identifier:
NCT02422485
First Posted: April 21, 2015
Last Update Posted: August 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Adam Boxer, University of California, San Francisco
  Purpose
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.

Condition Intervention Phase
Progressive Supranuclear Palsy Drug: Salsalate Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy

Resource links provided by NLM:


Further study details as provided by Adam Boxer, University of California, San Francisco:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • 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.

  • 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.

  • 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.


Other Outcome Measures:
  • Changes in concentration of cerebrospinal fluid (CSF) biomarkers [ Time Frame: 6 months ]
    Changes in the concentrations of cerebrospinal fluid (CSF) biomarkers

  • 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)]

  • 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.

  • 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;

  • Changes in sleep and activity levels [ Time Frame: 6 months ]
    Changes in actigraphic measures


Estimated Enrollment: 10
Study Start Date: April 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02422485


Contacts
Contact: Megan Frank, B.S. 415 476 -0671 Megan.Frank@ucsf.edu
Contact: Mary Koestler, RN, PhD 415 476 0661 mkoestler@memory.ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Megan Frank, BA    415-476-0671    megan.frank@ucsf.edu   
Contact: Mary Koestler, RN, PhD    415- 476- 0661    mkoestler@memory.ucsf.edu   
Principal Investigator: Adam Boxer, MD, PhD         
Sub-Investigator: Richard Tsai, MD, MBA         
United States, Oregon
OHSU Parkinson Center & Movement Disorder Program Recruiting
Portland, Oregon, United States, 97239
Contact: Eric Serres    503-494-0276    serres@ohsu.edu   
Principal Investigator: Joseph Quinn, MD         
Sponsors and Collaborators
Adam Boxer
Investigators
Principal Investigator: Adam Boxer, MD, PhD University of California, San Francisco
  More Information

Publications:
Schwab RS and England Jr AC. 1969. Projection techniques for evaluating surgery in Parkinson's disease. In: Gilingham FJ and Donaldson IML, eds. Third symposium on Parkinson's disease. Edinburgh: E & S Livingstone Ltd. 152-157.
Strauss E, Sherman EMS, Spreen O. 2006. A compendium of neuropsychological tests: Administration, norms and commentary. 3rd ed. New York: Oxford University Press.

Responsible Party: Adam Boxer, MD, PhD, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02422485     History of Changes
Other Study ID Numbers: Salsalate PSP
First Submitted: April 9, 2015
First Posted: April 21, 2015
Last Update Posted: August 1, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Adam Boxer, University of California, San Francisco:
Salsalate

Additional relevant MeSH terms:
Paralysis
Supranuclear Palsy, Progressive
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Tauopathies
Neurodegenerative Diseases
Eye Diseases
Salicylsalicylic acid
Sodium Salicylate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action