Treatment of Disturbed Sleep in Progressive Supranuclear Palsy (PSP)

Treatment Clinical Trial

Official title:

Treatment of Disturbed Sleep in Progressive Supranuclear Palsy (PSP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04014387
• Other study ID #: 20181608
• Status: Recruiting
• Phase: Phase 4
• Start date: June 2, 2019
• Est. completion date: May 15, 2025

Study information

• Verified date: October 2023
• Source: University of California, San Francisco
• Contact: Thomas Neylan, MD
• Phone: 415-750-6961
• Email: Thomas.Neylan[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 15, 2025
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Related Conditions & MeSH terms

• Supranuclear Palsy, Progressive
• Treatment

Intervention

Drug:
• Suvorexant
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.
• Zolpidem
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.
• Placebo oral capsule
Placebo (microcrystalline cellulose) capsules will be used.

Locations

Country	Name	City	State
United States	University of California- San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	US Department of Veterans Affairs

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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	Medication Satisfaction	Differences in satisfaction with the medication being taken. The Medication Satisfaction Scale is a study-specific customized satisfaction questionnaire of 3 questions each with a 5-point likert scale. The total range of scores is 3-15, with higher scores associated with greater medication satisfaction.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6)
Secondary	Adverse Events	The difference in the number of adverse events across each assessment week. The range of scores is 0 - undetermined, with greater scores associated with greater 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).
Secondary	Alertness	Change in alertness, which is assessed using question 8 of the Mayo Sleep Questionnaire - Informant. The range of scores is 0-10 with higher scores associated with greater alertness.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1)
Secondary	Sleepiness	Change in sleepiness, which is assessed using the Epworth Sleepiness Scale. The range of scores is 0-24 with higher scores associated with increased sleepiness.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).
Secondary	Insomnia	Change in subjectively reported insomnia assessed using the Insomnia Severity Index. The range of scores is 0-28 with higher scores associated with increased levels of insomnia.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).
Secondary	Anxiety	Change in anxiety levels assessed using the Generalized Anxiety Disorder - 7 (GAD-7) scale. The range of scores is 0-21 with higher scores associated with greater anxiety.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).
Secondary	Depression	Change in depression assessed using the PHQ-9 scale. The range of scores is 0-27 with higher scores associated with greater depression.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).
Secondary	Quality of Life Survey	Change in quality of life using the PSP Quality of life survey (PSP-QoL) , which assesses subjective quality of life specifically in individuals with Progressive Supranuclear Palsy. The range of scores is 0-100 with higher scores associated with poorer quality of life.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).
Secondary	Functionality	Change in functionality is assessed using the Tau functional scale. This is a questionnaire, which both the patient and caregiver work together to complete. The total range of scores is 0-124 with subscores for "motor experiences of daily living" (0-48 points), "Language/cognitive/behavioral" concerns (0-52) and "Other non-motor experiences of daily living" (0-24). In all cases, greater scores are associated with decreased independent functionality in those domains.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).
Secondary	Cognition	Change in cognition will be assessed using working memory measures of digits forward and digits backward, and executive function measures of categorical fluency and verbal fluency. The range of scores for digits forward and digits backward is 0-16 each, with higher scores indicating better cognition. The likely range of scores for the fluency measures are 0-60 with higher scores associated with better executive function. Rule violations and repetitions are also counted and scored with greater scores in these domains associated with poorer cognition.	7th day of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1)
Secondary	Slow wave sleep	Change in slow wave sleep will be assessed using a mobile EEG monitor called the Sleep Profiler (Advanced Brain Monitoring, Inc.). The amount of slow wave sleep will be measured as a percent of total sleep time, so the range of scores will be 0-100, with higher scores associated with greater amounts of slow wave sleep.	average of 5th-7th night of treatment for each of the two hypnotic drugs and placebo (weeks 2, 4 and 6) compared to baseline (week 1).