Treatment of Disturbed Sleep in Progressive Supranuclear Palsy (PSP)

NCT04014387 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 20181608
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Prior research has identified profound sleep disruption in individuals with PSP. Not only were these individuals sleeping relatively short periods at night, they were also not recuperating lost sleep during the day. Research also showed the relative preservation of a series of nuclei key in regulating wake and arousal. Investigators believe that therapeutically targeting wake promoting centers with a specific medication will improve sleep quality and overall well-being in PSP. To study this, investigators will be doing a double blind, within subject, remote clinical trial with 3 conditions: suvorexant- which targets a wake promoting system, zolpidem- a standard hypnotic that engages sleep promoting systems, versus placebo. Each condition will last 1 week and will be separated by a 1 week washout period on no sleep medications. Investigators will measure sleep patterns and daytime symptoms to determine if suvorexant, zolpidem, or both medications are safe and effective for treating sleep disturbances and improving overall well-being in PSP.

Conditions

Progressive Supranuclear Palsy(PSP); Insomnia

Outcome Measures

Primary Outcomes (2)

• Sleep Efficiency

  Change in sleep efficiency (as measured by actigraphy), this is a percentage of the time spent asleep compared to the total time in bed. The range of scores is 0-100, with higher scores associated with better sleep efficiency.

  average each of the 7 nights of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).

• Clinical Global Impression

  Change in Clinical Global Impression (CGI-C), this is a series of questions for the participant and caregiver which the neurologist utilizes to give a score of disease affects across a series of domains, which produces a single change score referenced to the baseline Clinical Global Impression of Disease Severity (CGI-ds). The range of scores is 1-7, with lower scores associated with better health.

  7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).

Secondary Outcomes (11)

• Medication Satisfaction

  7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6)

• Adverse Events

  total of events across the 7 days/nights of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).

• Alertness

  7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1)

• Sleepiness

  7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).

• Insomnia

  7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).

Study Arms (3)

Zolpidem Arm

ACTIVE COMPARATOR

Participants will be given one week of Zolpidem.

Drug: Zolpidem

Suvorexant Arm

ACTIVE COMPARATOR

Participants will be given one week of Suvorexant.

Drug: Suvorexant

Placebo Arm

PLACEBO COMPARATOR

Participants will be given one week of a placebo pill.

Drug: Placebo oral capsule

Interventions

Suvorexant DRUG

Suvorexant (Belsomra) is an FDA approved, dual orexin receptor antagonist. It is prescribed for insomnia, reducing time to sleep onset, and to maintain nighttime sleep.

Also known as: Belsomra

Suvorexant Arm

Zolpidem DRUG

Zolpidem (Ambien) is an FDA approved, Benzodiazepine Receptor agonist that has been extensively studied for the treatment of insomnia in older adults. It acts as a sedative and is typically prescribed to treat insomnia, reducing time to sleep onset, but may not alter the ability to maintain sleep.

Also known as: Ambien

Zolpidem Arm

Placebo oral capsule DRUG

Placebo (microcrystalline cellulose) capsules will be used.

Placebo Arm

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age at baseline.
• Documentation of a Progressive Supranuclear Palsy diagnosis as evidenced by one or more clinical features consistent with the Progressive Supranuclear Palsy phenotype as described in the Movement Disorder Society criteria or the NINDS-SPSP criteria.
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
• Have a diagnosis of PSP verified through co-enrollment in ARTFL, LEFFTDS or 4RTNI, or can show evidence of an accurate diagnosis of PSP to the satisfaction of the study team doctor (e.g. through review of medical records, and/or specific communication with a known medical doctor).
• Have an active caregiver who is willing and able to participate in this study
• Have a mailing address
• Have access to a phone
• Have stable medications (aside from sleep-modifying medications) for 4 weeks prior to actively starting the study
• Be free of sleep modifying medications for 1 week prior to actively starting the study
• Be willing to maintain a stable sleeping environment and their typical daily schedule for the duration of the 6-week study
• Resides in a US territory or state covered by our research study team.

You may not qualify if:

• Are pregnant, breastfeeding, or unwilling to practice birth control if appropriate during participation in the study.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Presence of a major psychiatric disorder aside from anxiety or depression.
• Presence of a medical condition other than PSP that could account for cognitive deficits (e.g. active seizure disorder, stroke, vascular dementia).
• Presence of current substance abuse or substance dependence.
• Presence of a significant systemic medical illness (e.g. significant cardiovascular, hematologic, renal, or hepatic disease).
• Presence of current medication likely to affect sleep outcomes: benzodiazepine receptor agonists (e.g. Zolpidem), Suvorexant, sedating antipsychotics (e.g. Quetiapine), sedating antihistamines (e.g. Benadryl), low dose sedating antidepressants (e.g. Trazodone, Doxepin), over the counter sleep-inducing medications (e.g. Tylenol-PM), neuroleptics in the phenothiazine and haloperidol families) which 1) the potential participant is not able/willing to stop taking for 1- week prior and for the 6-week duration of the study and/or 2) if removed could have a persistent effect beyond the 1-week wash-out period.
• Presence of insulin-dependent diabetes.
• History of mental retardation.
• Unable to communicate in English.

Sponsors & Collaborators

• University of California, San Francisco: lead
• US Department of Veterans Affairs: collaborator

Study Sites (1)

University of California- San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (1)

• Walsh CM, Ruoff L, Walker K, Emery A, Varbel J, Karageorgiou E, Luong PN, Mance I, Heuer HW, Boxer AL, Grinberg LT, Kramer JH, Miller BL, Neylan TC. Sleepless Night and Day, the Plight of Progressive Supranuclear Palsy. Sleep. 2017 Nov 1;40(11):zsx154. doi: 10.1093/sleep/zsx154.

  PMID: 29029214 BACKGROUND

MeSH Terms

Conditions

Supranuclear Palsy, Progressive; Sleep Initiation and Maintenance Disorders

Interventions

suvorexant; Zolpidem

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; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Thomas Neylan, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: July 10, 2019
• Study Start: June 2, 2019
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: September 1, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)