What side effects are associated with this type of intervention?

Common treatments for sleep disorders, such as benzodiazepines and non-benzodiazepine receptor agonists, often come with side effects including daytime sleepiness, dizziness, and cognitive impairment. Benzodiazepines carry risks of dependence, tolerance, and withdrawal symptoms. Non-benzodiazepine receptor agonists, while generally having a better safety profile, can still cause similar side effects and may also lead to complex sleep-related behaviors like sleepwalking. Other sedative medications, such as certain antidepressants and antipsychotics, can cause weight gain, motor restlessness, and mood changes. It is crucial to use these medications at the lowest effective dose and for the shortest duration necessary to minimize adverse effects.

What prior FDA approvals exist?

The FDA has approved several medications for the treatment of sleep disorders, including benzodiazepines (e.g., estazolam, flurazepam, quazepam, temazepam, triazolam) and non-benzodiazepine hypnotics (e.g., zolpidem, eszopiclone). These medications primarily work by enhancing the inhibitory action of GABA at the GABA-A receptor complex, promoting sedation. Additionally, sodium oxybate has been approved for the treatment of narcolepsy, particularly for cataplexy and disrupted nighttime sleep. Other treatments include melatonin receptor agonists like ramelteon and agomelatine, which are used for insomnia. These medications are relevant to the study of receptor binding in brain regions associated with pain inhibition and abuse liability due to their mechanisms of action and potential effects on receptor function.

What other types of research exist?

Promising novel alternatives for sleep disorders patients include dual orexin receptor antagonists, such as those derived from substituted lactams, which have shown improved metabolic stability and CNS drug-like properties. Additionally, N-aryl-2-phenylcyclopropanecarboxamide compounds have demonstrated potent in vitro activity and oral efficacy in animal sleep studies, suggesting potential benefits for human use. These alternatives may offer effective treatment options with a focus on reducing abuse liability and improving sleep quality.

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Sleep Disturbance + Study Drug for Sleep Disorders (Sleep-MOR Trial)

Phase 2

Recruiting

Led By Michael T Smith, PhD

Research Sponsored by Johns Hopkins University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be between 18 and 65 years old

Must not have

BMI >35

Acute pain

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 90 minutes on day 3 of inpatient visit

Summary

This trial tests how different types of sleep problems affect the brain's response to a pain-relief drug and its potential for abuse. Healthy subjects will have their sleep patterns manipulated and then undergo brain scans and pain tests. The goal is to see if poor sleep makes pain drugs less effective or more likely to be abused.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects depend on the specific medication given but may include drowsiness or alertness (for sedatives and stimulants respectively), addiction risk (opioids), changes in mood or appetite (cannabinoids) and typical over-the-counter medication risks like stomach upset.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My BMI is over 35.

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I am currently experiencing severe pain.

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I have not had significant health or mental health issues in the past 6 months, nor do I have a history of bipolar, psychotic disorders, or seizures.

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I have had a head injury that made me unconscious for more than 3 minutes.

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I have experienced chronic pain for a long time.

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I do not have major brain or nerve diseases like lupus or MS.

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I have been experiencing significant emotional or mental distress before being admitted.

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I have been diagnosed with a sleep disorder.

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I have been exposed to high levels of radiation before this study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 90 minutes on day 3 of inpatient visit

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 90 minutes on day 3 of inpatient visit

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 90 minutes on day 3 of inpatient visit for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Drug Effects as assessed by the Visual Analog Scale

Percent change in receptor binding potential from PET scan

The monetary valuation in dollars of the study medication as assessed by the Drug or Money Multiple Choice Questionnaire

+1 more

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Sleep FragmentationExperimental Treatment2 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 DisruptionExperimental Treatment2 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 SleepActive Control2 Interventions

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

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for sleep disorders include pharmacologic agents and behavioral interventions. Pharmacologic treatments often involve benzodiazepine receptor agonists, which enhance the effect of the neurotransmitter GABA, leading to sedative and hypnotic effects. These drugs can reduce sleep latency and increase total sleep time but may have side effects like daytime sleepiness and potential for dependence. Behavioral interventions, such as cognitive-behavioral therapy for insomnia (CBT-I), focus on changing sleep habits and thought patterns to improve sleep quality. Understanding these mechanisms is crucial for patients, as it helps tailor treatments to individual needs, potentially improving efficacy and minimizing side effects. In the context of receptor binding and pain inhibition, as studied in certain trials, these treatments may also impact pain perception and abuse liability, highlighting the importance of a comprehensive approach to managing sleep disorders.

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