Le Rêve 3.0: A Double-Blind, Placebo-Controlled, Randomized, Crossover Investigational Study to Determine if Defined CBD, a Capsule With a Custom Formulation of Cannabidiol (CBD) and Terpenes, Influences Sleep Physiology
Overview
- Phase
- Phase 2
- Intervention
- Defined CBD
- Conditions
- Insomnia
- Sponsor
- Defined Research
- Enrollment
- 125
- Locations
- 1
- Primary Endpoint
- Percentage of Time Spent in the Combination of Slow Wave Sleep (SWS) and Rapid Eye Movement (REM) Sleep
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
Insomnia is a disorder in which people have inadequate or poor-quality sleep due to a number of factors, such as difficulty falling asleep, waking up frequently during the night with difficulty returning to sleep, waking up too early in the morning, or having unrefreshing sleep. Defined CBD is a capsule composed of highly purified (>99.9%) hemp-derived cannabidiol (CBD) and terpenes produced as a potential sleep aid for people with insomnia. This product contains no detectable Delta-9-tetrahydrocannabinol (Delta-9-THC). This trial is specifically designed to evaluate the efficacy of Defined CBD on sleep physiology in people with insomnia.
Detailed Description
Our research study aims to test the effects of a highly purified CBD product on the structure and function of sleep physiology. In a survey by Consumer Reports, \~40% of adults who reported trying CBD said they used it to help them sleep, and a majority of those people said it worked. Nonetheless, to this date a rigorous, properly-controlled, and well-powered study to determine if CBD influences sleep physiology has simply never been reported in the scientific literature. The Le Rêve 3.0 study is designed to fill this important void in scientific knowledge. We hypothesize that a novel CBD-based formulation in the form of an orally administered capsule will positively impact sleep physiology in subjects with insomnia. The capsule we will test is composed of \>99.9% purity hemp-derived CBD with a custom chemical formulation that also contains low concentrations (1 mg each) of highly purified (\>98%) forms of the terpenes linalool, myrcene, phytol, limonene, alpha-terpinene, alpha-terpineol, alpha-pinene, and beta-caryophyllene. Preclinical studies in animals have shown that these terpenes are sedating, but their potential effects on sleep physiology in humans have not been established. This product contains no detectable Delta-9-THC. The Le Rêve 3.0 study will involve a cross-over design in which study participants will cycle through two independent treatments each for four weeks (Treatment 1: Placebo; Treatment 2: Defined CBD). The study participants will initially be randomized with respect to the treatment group, and all participants will be cycled through each of the two treatments. We will use a double-blind design in which the investigator and study participants will both be blinded to the treatments. Baseline data for each participant will be collected for two weeks prior to initiating treatments, as well as for a one-week washout period following each treatment arm. The entire study will last 12 weeks. The primary objective of the study is to determine if Defined CBD influences objective measures of sleep physiology. Primary sleep physiology data will be obtained in a completely unbiased manner from a non-invasive sleep-tracking wristband, called "Whoop" (https://www.whoop.com), that electronically collects and transmits sleep data from study participants in the comfort of their own beds. The wristband collects hundreds of data points per second from a 3-axis accelerometer, 3-axis gyroscope, and heart rate sensor. The wristband can accurately measure latency to fall asleep, total sleep time, sleep fragmentation, as well as the time spent in each sleep stage \[Light, Slow Wave (Deep), Rapid Eye Movement (REM), and Awake\]. The wristband also collects data using photoplethysmography (PPG), a technique that involves measuring blood flow by assessing superficial changes in blood volume. Heart rate, heart rate variability, and respiratory rate, can all be derived from PPG data, and all of these metrics are used in Whoop's sleep detection and staging algorithms. Importantly, two recent publications, published independently from Whoop, show that data on sleep stages collected from the Whoop device are highly accurate and correlate well with polysomnography (PSG), the gold-standard of sleep tracking used in clinical studies conducted in sleep clinics. The secondary objective of the study is to determine if Defined CBD influences subjective measures of sleep physiology. We will collect this subjective data from study participants in the form of a brief five-minute survey that will be completed on their smartphone at the end of each treatment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Has provided a signed and dated informed consent form.
- •Presence of chronic insomnia defined as self-reported difficulty initiating (latency to persistent sleep \>30 min) and/or maintaining sleep (\>30 mins awake during the middle of the night, or waking \>30 mins before desired waking time on three or more nights per week) for at least 3 months.
- •Insomnia Severity Index score \>
- •Male or female aged 25-70 years.
- •Is willing to comply with all study procedures throughout the entire study, including:
- •Wearing a sleep-tracking device on their wrist throughout entire clinical study.
- •Ensuring that the sleep-tracking device is connected to their smartphone via Bluetooth on a daily basis so that sleep data can be collected on a daily basis.
- •Ensuring that the sleep-tracking device is charged before going to bed each night, ensuring that sleep data can be collected on a daily basis.
- •Is willing to receive and respond to daily text (SMS) notifications for the duration of the entire clinical study.
- •During the treatment phases of the study, is willing to take the treatment for at least four nights in each week.
Exclusion Criteria
- •Self-reported body mass index \> 32 calculated from patient's height (m) and weight (kg); weight (kg)/square height (m²).
- •Insomnia associated with clinically diagnosed sleep apnea (AHI greater than 15 events/hour), or movement disorders such as restless legs, periodic limb movement (PLM) (greater than 30 events/hour or greater than five events/hour with associated PLM arousals).
- •Are currently participating in a formal behavioral therapy program to facilitate sleep.
- •History of epilepsy or seizures.
- •History of liver disease.
- •Serious head injury or stroke within the past year.
- •Psychiatric disorders including major depression, bipolar, anxiety, or schizophrenia.
- •History of suicide attempt or current suicide ideation.
- •Evidence of any clinically significant, severe or unstable, acute or chronically progressive medical or surgical disorder (including planned medical procedures that may impact sleep), or any condition that may interfere with the absorption, metabolism, distribution, or excretion of the study drug.
- •Patients with a history of cardiovascular disease including poorly controlled hypertension, ischemic heart disease, arrhythmia, or severe heart failure.
Arms & Interventions
Defined CBD
Defined CBD will be administered as two small capsules that will be taken orally with a glass of water one hour before bedtime that contain a total of 300 mg CBD and 8 mg terpenes. Participants will take the treatment on a minimum of four nights per week, over a total of four-weeks.
Intervention: Defined CBD
Placebo
The placebo control will be administered as two small capsules that will be taken orally with a glass of water one hour before bedtime that do not contain any CBD or terpenes. Participants will take the treatment on a minimum of four nights per week, over a total of four-weeks. The Placebo capsules will look and smell identical to the Defined CBD capsules.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of Time Spent in the Combination of Slow Wave Sleep (SWS) and Rapid Eye Movement (REM) Sleep
Time Frame: Participants were assessed for treatment with CBD-terpenes and placebo, each for a treatment period of four weeks. Participants took the treatment (CBD-terpenes or Placebo) for at least four nights per week over the entire four week treatment period.
The primary endpoint is the percentage of time spent in slow wave (Deep) and REM sleep as quantified by a non-invasive wrist-worn sleep-tracking device called Whoop.
Secondary Outcomes
- Objective Secondary Outcome Measures of Sleep Physiology(Four weeks)
- Subjective Secondary Outcome Measure of Sleep Physiology(Participants were assessed for treatment with CBD-terpenes and placebo, each for a treatment period of four weeks. Participants took the treatment (CBD-terpenes or Placebo) for at least four nights per week over the entire four week treatment period.)