Sleep Disturbance + Study Drug for Sleep Disorders

(Sleep-MOR Trial)

Overseen By Nicholas G Wolf, BA

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Antidepressants, Neuroleptics, Opioids, others

Disqualifiers: Chronic pain, Sleep disorder, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 3

Duration: 4 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how common sleep issues, like interrupted sleep and frequent waking, affect the brain's response to a study drug used for pain relief and its potential for misuse. Participants will experience different sleep conditions, including disrupted and undisturbed sleep, to assess how these affect the drug's impact on pain and its side effects. The trial seeks healthy individuals who sleep well at night, have previously been prescribed opioids for pain, and have low caffeine intake. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that participants have not used certain medications like antidepressants, neuroleptics, sedative hypnotics, and opioids in the last three months. If you are currently taking these, you would need to stop before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sleep medications are generally safe. In a previous study, only 12% of participants experienced side effects, none of which were serious. This finding is encouraging for those considering joining a trial. Additionally, melatonin receptor agonists, a type of sleep medication, are known to cause the fewest side effects. This suggests that the study drug being tested might also be easy to tolerate. However, since this is a Phase 2 trial, researchers are still carefully monitoring the treatment's safety. Participants should feel free to ask questions and share any concerns during the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this trial because it explores how different kinds of sleep interruptions impact sleep disorders. Unlike most treatments for sleep disorders that focus on medications like benzodiazepines or melatonin, this trial investigates the effects of sleep disruptions such as forced awakenings and microarousals, similar to sleep apnea. By comparing these disruptions to undisturbed sleep, researchers hope to better understand the physiological impacts and potentially develop new strategies for managing sleep disturbances, moving beyond traditional medication-based approaches.

What evidence suggests that this trial's treatments could be effective for sleep disorders?

This trial will compare the effects of different sleep conditions on medication effectiveness. Studies have shown that sleep problems can affect how well people respond to medication, including pain relievers. Disrupted sleep might reduce the effectiveness of these medications. Research suggests that certain sleep medications, especially when combined with antidepressants, can help with conditions like major depression and insomnia. However, one study found no major improvements in sleep problems after using prescription sleep medications for one or two years. Thus, while sleep medications can be helpful, their effectiveness can vary, especially if the root cause of sleep issues isn't addressed. ^{1 2 3 4 6}

Who Is on the Research Team?

Eric C Strain, MD

Principal Investigator

Johns Hopkins University

Naresh Punjabi, MD

Principal Investigator

Johns Hopkins University

Claudia Campbell, PhD

Principal Investigator

Johns Hopkins University

Patrick H Finan, PhD

Principal Investigator

Johns Hopkins University

Jeannie Leoutsakos, PhD

Principal Investigator

Johns Hopkins University

Michael T Smith, PhD

Principal Investigator

Johns Hopkins University

Hiroto Kuwabara, MD

Principal Investigator

Johns Hopkins University

Alexandra Kearson, BA

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-48 who sleep well (6.5 to 8.5 hours a night with good quality), don't smoke or use nicotine, and consume little caffeine. They must have had some exposure to opioids in the past but can't be overweight, have sleep disorders, metal implants unsafe for MRI, significant neurological diseases, recent serious medical issues or substance abuse history.

Inclusion Criteria

You drink two cups of coffee or less per day.

You sleep between 6.5 and 8.5 hours per night and have a sleep efficiency of at least 85%.

You have taken opioids for pain in the past.

Exclusion Criteria

My BMI is over 35.

I am currently experiencing severe pain.

You feel uncomfortable in small, enclosed spaces.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants undergo sleep manipulation and study drug administration to assess receptor function, analgesia, and abuse liability

4 days

1 visit (inpatient stay)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Within-Subject test of blinded study medication

Trial Overview The study tests how different types of sleep disturbances affect the brain's response to various drugs including stimulants, benzodiazepines, opioids, cannabinoids and pain relievers compared to placebo. It looks at drug effects on pain relief and potential for misuse under normal sleep conditions versus disrupted sleep.

How Is the Trial Designed?

Group I: Sleep Fragmentation Experimental Treatment 2 Interventions

The Sleep fragmentation condition will be conducted on two consecutive nights. Subjects are provided an 8-hour sleep opportunity during which their sleep will be disturbed by microarousals that simulate sleep apnea.

Group II: Sleep Continuity Disruption Experimental Treatment 2 Interventions

The Sleep Continuity Disruption condition will be conducted on two consecutive nights. An 8-hour sleep opportunity period will be disturbed by several forced awakenings at random intervals during which no sleep is permitted.

Group III: Undisturbed Sleep Active Control 2 Interventions

An 8-hour period of undisturbed sleep is permitted on each night.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Cognitive-behavioral therapy for insomnia (CBT-I) helps correct the common issue of individuals underreporting their sleep, as shown in a study of 60 adults with insomnia, where self-reported sleep improved after treatment.

Although there were no significant changes in objective sleep measurements from polysomnography (PSG), a decrease in stage N1 sleep was linked to better self-reported sleep quality, suggesting that CBT-I may enhance the accuracy of sleep estimation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The discrepancy between subjective and objective measures of sleep in older adults receiving CBT for comorbid insomnia. Lund, HG., Rybarczyk, BD., Perrin, PB., et al.[2022]

In a study of 405 sleep studies, it was found that using multiple psychotropic medications (like antidepressants combined with anticonvulsants or antipsychotics) does not significantly harm sleep architecture, suggesting these combinations may be safe for sleep health.

Antidepressants alone were linked to longer REM latency and a higher prevalence of periodic limb movement disorder, but the addition of anticonvulsants or antipsychotics may help protect against these sleep-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effects of psychotropic medications on sleep architecture: a retrospective review of diagnostic polysomnography sleep parameters. Ghossoub, E., Geagea, L., Kobeissy, F., et al.[2022]

In a review of 24 studies involving 2417 older adults with insomnia, sedative hypnotics showed statistically significant improvements in sleep quality, total sleep time, and reduced nighttime awakenings, but the overall effect size was small.

However, the use of sedatives was associated with a significantly higher risk of adverse events, including cognitive impairment and daytime fatigue, raising concerns about their safety in older adults, especially those at risk for falls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. Glass, J., Lanctôt, KL., Herrmann, N., et al.[2022]

In a comparison of sleep disorder medication patterns, the study found that 11.7% of the French population used psychotropic medications, significantly higher than the 5.5% in Quebec, indicating a notable difference in medication consumption between the two regions.

Both studies revealed that the majority of sleep-promoting medications were prescribed for long durations (over a year) and that general practitioners were responsible for about 80% of these prescriptions, highlighting a common trend in prescribing practices despite the differences in overall consumption rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychotropic medication and insomnia complaints in two epidemiological studies. Ohayon, MM., Caulet, M.[2022]

In a review of seven randomized placebo-controlled trials involving 429 patients, trazodone was found to significantly improve perceived sleep quality compared to placebo, although it did not enhance sleep efficiency or other objective sleep measures.

Trazodone effectively reduced the number of awakenings during the night, indicating its potential for improving sleep maintenance, while demonstrating good tolerability in short-term use for treating insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials. Yi, XY., Ni, SF., Ghadami, MR., et al.[2022]

In a study of 4221 participants aged 45 to 75, the intake of drugs labeled as sleep disturbing showed little to no association with self-reported nocturnal sleep disturbances, suggesting that the information from drug labels may not apply well to the general population.

The analysis indicated that the prevalence ratios for sleep disturbances did not significantly increase with the number of sleep disturbing drugs taken, raising questions about the reliability of clinical trial data in predicting real-world effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do patients with intake of drugs labelled as sleep disturbing really sleep worse? A population based assessment from the Heinz Nixdorf Recall Study. Lehnich, AT., Kowall, B., Kuß, O., et al.[2021]

In a study of 987 Japanese adults with chronic insomnia, ramelteon 8 mg significantly reduced the time it took for patients to fall asleep (sleep latency) after just one week of treatment, compared to a placebo.

Ramelteon also improved total sleep time and sleep quality, and was well tolerated with no evidence of rebound insomnia after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of subjective efficacy and safety of ramelteon in Japanese subjects with chronic insomnia. Uchiyama, M., Hamamura, M., Kuwano, T., et al.[2022]

A study involving 238 women who started prescription sleep medications found no significant improvement in self-reported sleep disturbances after 1 or 2 years compared to 447 women who did not use these medications.

Both groups reported similar levels of difficulty initiating sleep, waking frequently, and early morning awakening, suggesting that long-term use of sleep medications may not be effective in reducing sleep disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription medications for sleep disturbances among midlife women during 2 years of follow-up: a SWAN retrospective cohort study. Solomon, DH., Ruppert, K., Habel, LA., et al.[2021]

In a meta-analysis of 34 studies involving 1392 subjects, pharmacological placebos significantly improved subjective sleep onset latency and total sleep time compared to untreated groups, indicating that even inactive treatments can influence sleep outcomes.

No significant sleep changes were observed in psychological placebo groups, suggesting that the type of placebo may affect the magnitude of sleep improvements, and further research is needed to clarify these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of sleep changes in control groups of insomnia treatment trials. Bélanger, L., Vallières, A., Ivers, H., et al.[2007]

Melatonin receptor agonists have the lowest rate of adverse events (43.1 per 1000), while non-benzodiazepine benzodiazepine receptor agonists have the highest (255.0 per 1000), indicating a significant difference in safety profiles among insomnia medications.

Benzodiazepines showed the highest efficacy in improving sleep outcomes with an effect size of 1.94, while melatonin receptor agonists had the lowest efficacy (0.109), suggesting that histamine antagonists may offer the best risk-benefit ratio for treating insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative short-term safety and efficacy of hypnotics: A quantitative risk-benefit analysis. Cheung, JMY., Scott, H., Muench, A., et al.[2023]

In two multicenter safety studies involving nearly 4,000 patients treated with zolpidem for insomnia, only 8.9% and 7.2% reported adverse events, indicating a relatively low incidence of side effects.

The most common adverse effects were related to the central nervous system, such as somnolence and confusion, but no new serious adverse events were identified, supporting the established safety profile of zolpidem.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety profile of zolpidem: two studies of 3805 patients by Swiss practitioners]. Ganzoni, E., Gugger, M.[2018]

The NAP Study is a large-scale clinical trial involving 1224 veterans with PTSD, comparing the efficacy of three insomnia medications (trazodone, eszopiclone, and gabapentin) against a placebo over 12 weeks, aiming to find effective treatments for PTSD-related insomnia.

The study features an adaptive design that allows for real-time adjustments based on interim results, potentially enhancing the statistical power of the remaining treatment comparisons and guiding future research on biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of the National Adaptive Trial for PTSD-related Insomnia (NAP Study), VA Cooperative Study Program (CSP) #2016. Krystal, JH., Chow, B., Vessicchio, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03680287

Study Details | NCT03680287 | Effects of Sleep Disruption ... The central scientific premise of the proposed study is that sleep disruption (SD) will influence individuals' subjective response to blinded medication ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7069777/

Sleep Disturbance Predicts Less Improvement in Pain ... Sleep disturbance may limit improvement in pain outcomes if not directly addressed in treatment. Moreover, sleep problems may be exacerbated by opioid ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12131207/

Efficacy and safety of each class of sleep medication for major ... Combination therapy with antidepressants and sleep medications is a promising candidate treatment for major depressive disorder (MDD) with insomnia.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04299490?tab=table

Effects of Experimental Sleep Disturbances on Receptor ... The Sleep Continuity Disruption condition will be conducted on two consecutive nights. An 8-hour sleep opportunity period will be disturbed by several forced ...

5. withpower.com withpower.com/trial/phase-3-sleep-wake-disorders-10-2020-feeb6

Sleep Disturbance + Study Drug for Sleep Disorders · Info ... A study involving 238 women who started prescription sleep medications found no significant improvement in self-reported sleep disturbances after 1 or 2 years ...

6. tandfonline.com tandfonline.com/doi/full/10.1080/27697061.2023.2203221

The Safety and Comparative Effectiveness of Non ... All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in ...