Suvorexant for Sleep Disturbances in PSP

Overseen By Christine Walsh, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Benzodiazepines, Sedating antipsychotics

Disqualifiers: Pregnancy, Major psychiatric disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two medications, Suvorexant (Belsomra) and Zolpidem (Ambien), affect sleep disturbances in individuals with Progressive Supranuclear Palsy (PSP), a condition that severely disrupts sleep. Researchers aim to determine if either medication can improve sleep quality and overall well-being. Participants will try each treatment and a placebo for one week each, with a one-week break without sleep medications in between. Suitable candidates for this trial include those with a confirmed PSP diagnosis, who experience sleep issues, and can maintain a stable sleep routine. As a Phase 4 trial, this study involves FDA-approved treatments and aims to further understand their benefits for more patients.

Do I have to stop taking my current medications to join the trial?

You need to stop taking sleep-modifying medications for 1 week before starting the study and cannot take them during the 6-week study. Other medications must be stable for 4 weeks before starting the study.

What is the safety track record for these treatments?

Research has shown that suvorexant has been tested for safety in people with Alzheimer's disease, suggesting it might be safe for humans. These studies found no major safety issues, which is promising for its use in other conditions like progressive supranuclear palsy (PSP).

Zolpidem, a well-known sleep aid, is commonly used for sleep problems and has also shown improvements in PSP symptoms. However, older patients might experience side effects, so age can affect its tolerance.

Both treatments have been studied in humans for a considerable time, providing substantial safety information. Always consult a doctor to understand how these treatments might work personally. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Suvorexant for sleep disturbances in Progressive Supranuclear Palsy (PSP) because it targets orexin receptors, which play a key role in regulating sleep-wake cycles. Unlike traditional sleep aids like Zolpidem, which primarily enhance the effects of GABA to induce sleep, Suvorexant's mechanism offers a novel approach that may better address the unique sleep challenges in PSP patients. This distinct action could lead to improved sleep quality and potentially fewer side effects, providing a promising alternative for those affected by this condition.

What evidence suggests that this trial's treatments could be effective for sleep disturbances in PSP?

Research has shown that suvorexant, a medication approved for treating insomnia, helps people fall asleep faster and sleep longer by affecting parts of the brain that maintain wakefulness. In this trial, participants will receive either suvorexant or zolpidem to address sleep problems in Progressive Supranuclear Palsy (PSP), a condition characterized by serious sleep issues. Zolpidem, another medication in this trial, promotes sleep by targeting a specific part of the brain and has improved sleep, movement, and eye control in some PSP patients. Both treatments have been studied for their potential to improve sleep quality, making them promising options for addressing sleep problems in PSP. ^{2 3 6 7 8}

Who Is on the Research Team?

Thomas Neylan, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults with Progressive Supranuclear Palsy (PSP) who have stable medications, a caregiver, and can comply with study requirements. Participants must not be on sleep-modifying meds prior to the study or have conditions that could affect safety/data quality.

Inclusion Criteria

You have been diagnosed with PSP by participating in certain research studies or by providing evidence of an accurate diagnosis to the study doctor.

Be willing to maintain a stable sleeping environment and their typical daily schedule for the duration of the 6-week study

I haven't taken any sleep medications for the last week.

Exclusion Criteria

I am not taking sleep-affecting medications or can stop them for 7 weeks.

I have diabetes that requires insulin.

You have a history of intellectual disability.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a double-blind, within-subject trial with three conditions: suvorexant, zolpidem, and placebo, each lasting 1 week, separated by a 1-week washout period.

6 weeks

Remote monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo oral capsule
• Suvorexant
• Zolpidem

Trial Overview The trial tests if suvorexant or zolpidem improves sleep in PSP compared to a placebo. It's a double-blind study where each treatment lasts one week with washout periods in between. Sleep patterns and daytime symptoms are measured to assess effectiveness.

How Is the Trial Designed?

Group I: Zolpidem Arm Active Control 1 Intervention

Participants will be given one week of Zolpidem.

Group II: Suvorexant Arm Active Control 1 Intervention

Participants will be given one week of Suvorexant.

Group III: Placebo Arm Placebo Group 1 Intervention

Participants will be given one week of a placebo pill.

Suvorexant is already approved in United States, Japan for the following indications:

Approved in United States as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Approved in Japan as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

US Department of Veterans Affairs

Collaborator

Trials

881

Recruited

502,000+

Published Research Related to This Trial

In a study of 1126 patients with metastatic bone disease, zoledronic acid (ZOL) showed a significant improvement in overall survival for 38% of patients with elevated baseline NTX levels, indicating its potential effectiveness in advanced cases.

While ZOL did not show a general survival advantage across all patients, its benefits were particularly noted in those with aggressive disease characteristics, suggesting that ZOL may be especially beneficial for patients with advanced metastatic bone disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features-An exploratory analysis of placebo-controlled trials. Coleman, RE., Lipton, A., Costa, L., et al.[2022]

This trial will assess the efficacy of suvorexant, an FDA-approved sleep aid, in reducing nighttime wakefulness and delirium in 120 older cardiac surgery patients in the ICU.

The study aims to determine if suvorexant can improve sleep quality and reduce the incidence of postoperative delirium, which is important for recovery in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. Azimaraghi, O., Hammer, M., Santer, P., et al.[2021]

Suvorexant, the first orexin receptor antagonist approved by the FDA for treating insomnia, has been shown to effectively induce and maintain sleep in adult and elderly patients over treatment periods of up to 12 months.

While the FDA approved doses of 5, 10, 15, and 20 mg due to concerns about safety and next-morning effects like somnolence and unusual behaviors, suvorexant represents a novel approach to insomnia treatment, potentially leading to new therapies targeting orexin receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. Jacobson, LH., Callander, GE., Hoyer, D.[2015]

In a study involving 1960 patients with newly diagnosed multiple myeloma, both zoledronic acid (ZOL) and clodronate (CLO) were found to be well tolerated over a median follow-up of 5.9 years, with similar rates of acute renal failure between the two treatments.

The incidence of osteonecrosis of the jaw (ONJ) was low overall but significantly higher in the ZOL group (3.7%) compared to the CLO group (0.5%), indicating a potential safety concern with ZOL, particularly after dental procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results. Jackson, GH., Morgan, GJ., Davies, FE., et al.[2022]

In a Phase I trial of suramin for hormone-refractory prostate cancer, 22% of patients on low doses and 32% on high doses experienced adrenal cortical insufficiency, indicating a dose-dependent risk of glucocorticoid and mineralocorticoid insufficiency.

Long-term glucocorticoid insufficiency was observed in 20% of patients tested more than 90 days after stopping suramin, suggesting that patients on high doses should receive appropriate hormone replacement therapy to manage potential adrenal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mineralocorticoid insufficiency due to suramin therapy. Kobayashi, K., Weiss, RE., Vogelzang, NJ., et al.[2019]

Suvorexant, an orexin receptor antagonist, significantly improved sleep parameters in healthy young men, with all doses (10 mg, 50 mg, and 100 mg) showing better sleep compared to placebo, particularly in reducing the time to persistent sleep and wake after sleep onset.

While suvorexant was generally well tolerated, higher doses (50 mg and 100 mg) showed some next-day residual effects, such as reduced alertness and slower reaction times, indicating a need for careful dosing in potential therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sun, H., Kennedy, WP., Wilbraham, D., et al.[2022]

Suvorexant, a dual orexin receptor antagonist approved for insomnia, is primarily metabolized in the body with 90% of its radioactivity recovered after administration, indicating effective absorption and elimination.

The drug mainly inhibits CYP3A4 and CYP2C19 enzymes but is unlikely to cause significant drug interactions at clinical doses due to low plasma concentrations, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans. Cui, D., Cabalu, T., Yee, KL., et al.[2017]

The combination of estramustine phosphate (EMP) at 900 mg/m2 and paclitaxel at 225 mg/m2 is well tolerated in women with solid tumors, with significant antitumor activity observed against breast and ovarian cancers.

The maximum-tolerated dose was identified as EMP 1,200 mg/m2, which caused severe side effects like nausea and vomiting, leading to the use of a lower dose (900 mg/m2) in further studies without affecting paclitaxel pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacologic study of estramustine phosphate and short infusions of paclitaxel in women with solid tumors. Garcia, AA., Keren-Rosenberg, S., Parimoo, D., et al.[2017]

Suvorexant (Belsomra®) is a new sleep medication that works by blocking orexin neurons, leading to a rapid onset of sleep, and is effective at a prescribed dose of 10 mg before bedtime.

A highly sensitive urine assay was developed to accurately identify and quantify suvorexant, demonstrating excellent precision and stability, which is crucial for monitoring its use due to potential misuse and interactions with other sedatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). Sullinger, S., Bryand, K., Kerrigan, S.[2017]

In a phase III trial involving 308 patients with untreated high-risk multiple myeloma, zoledronic acid significantly improved both overall survival (67% vs. 48%) and progression-free survival (66% vs. 52%) compared to the control group after a median follow-up of nearly 70 months.

The treatment was well tolerated, with no reported cases of renal impairment or osteonecrosis of the jaw, indicating that zoledronic acid can be safely integrated into the treatment regimen for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation. Avilés, A., Neri, N., Huerta-Guzmán, J., et al.[2021]

In a study of 1,655 multiple myeloma patients, those treated with zoledronic acid (ZOL) experienced significantly lower rates of skeletal-related events (SREs) and mortality compared to those who did not receive bisphosphonate therapy.

Patients who maintained longer treatment persistency with ZOL (≥1.5 years) had a much lower incidence of SREs and fractures, highlighting the importance of consistent treatment for maximizing clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistency with zoledronic acid is associated with clinical benefit in patients with multiple myeloma. Henk, HJ., Teitelbaum, A., Perez, JR., et al.[2018]

In a study of 22 patients with high-risk metastatic hormone-sensitive prostate cancer, treatment with abiraterone acetate plus androgen deprivation therapy (AAP + ADT) resulted in significantly longer prostate-specific antigen progression-free survival (PSA-PFS) compared to combined androgen blockade (CAB), with PSA-PFS not reached in the AAP group versus 15.1 months in the CAB group.

The AAP group also achieved lower serum PSA levels more quickly, with times to reach PSA ≤0.2 ng/ml and ≤0.1 ng/ml being significantly shorter than in the CAB group, indicating that AAP may offer better clinical efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of Abiraterone Acetate Plus Prednisolone and Combined Androgen Blockade in High-risk Metastatic Hormone-Sensitive Prostate Cancer]. Yasukawa, H., Ikehata, Y., Tsuboi, Y., et al.[2021]

Positive airway pressure (PAP) therapy is the gold standard for treating sleep-disordered breathing, significantly reducing apnea-hypopnea index (AHI) and improving patient quality of life, but many patients struggle with adherence due to discomfort.

Emerging treatments like the hypoglossal nerve stimulator and phrenic nerve stimulator offer promising alternatives by directly stimulating nerves to alleviate airflow obstruction and stabilize breathing patterns, respectively, thus improving AHI severity and quality of life for patients with obstructive and central sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Treatment of Sleep-Disordered Breathing. Lou, BX., Greenberg, H., Korotun, M.[2021]

Abiraterone, enzalutamide, and radium-223 have been shown to significantly improve both radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC), based on phase 3 clinical trials.

Each treatment has distinct adverse effects: enzalutamide increases the risk of seizures, abiraterone can lead to mineralocorticoid excess, and radium-223 is associated with myelosuppression, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy Update for Metastatic Castration-Resistant Prostate Cancer. Dinh, JA., Baker, D., Chahal, M.[2017]

In a study of 1052 patients with metastatic castration-sensitive prostate cancer, apalutamide combined with androgen-deprivation therapy significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo plus ADT.

While apalutamide exposure did not correlate with improved survival outcomes, higher exposure levels were linked to an increased risk of skin rash and pruritus, suggesting that dose adjustments may be beneficial to manage these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study. T'jollyn, H., Ackaert, O., Chien, C., et al.[2022]

Citations

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Treatment of Disturbed Sleep in Progressive Supranuclear... Suvorexant (Belsomra) is an FDA approved, dual orexin receptor antagonist. It is prescribed for insomnia, reducing time to sleep onset, and to ...

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Treatment of Disturbed Sleep in Progressive Supranuclear ... Investigators believe that therapeutically targeting wake promoting centers with a specific medication will improve sleep quality and overall well-being in PSP.

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FEATURED STUDY: Treatment of Disturbed Sleep in PSP Researchers hope to answer the question: “Can We Improve Sleep in PSP?” The study will test the effectiveness of two sleep medications. While there is no ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4591519/

Suvorexant in insomnia: efficacy, safety and place in therapy Suvorexant is the first DORA to be approved and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20265559

A Study of the Safety and Effectiveness of Suvorexant (MK- ... The purpose of this study is to examine the safety and effectiveness of suvorexant (MK-4305) to improve sleep in individuals who have Alzheimer's disease.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02750306

NCT02750306 | Safety and Efficacy of Suvorexant (MK- ... This study aims to examine the safety and efficacy of suvorexant (MK-4305) to improve sleep in individuals with Alzheimer's disease (AD).

7. researchgate.net researchgate.net/publication/382381216_Treatment_of_Disturbed_Sleep_in_Progressive_Supranuclear_Palsy_Study_Protocol_of_a_Fully_Remote_Clinical_Trial

Study Protocol of a Fully Remote Clinical Trial Hypothesis: Ho3) Suvorexant, relative to zolpidem, will produce greater improvement in sleep e ciency,. greater changes in clinical global ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11263316/

Pharmacotherapies for the Treatment of Progressive ... This review summarizes the therapies that have been studied and those that are currently undergoing clinical trials for the treatment of PSP.