Combined Effects of Prunus Cerasus and Apocynum Venetum On Sleep and Anxiety in Adults With Insomnia

The rationale for this study is to determine the effect of a consumer-grade, unique formula called Sip2Sleep®, which is a combination of Montmorency tart cherry extract and Venetron®, a patented, purified, powdered extract derived from the Rafuma leaf, Apocynum venetum, on sleep disturbance in adults. Because this product is currently available in the OTC market across the United States, a consumer-driven, decentralized observational clinical research study is well-suited for examining the effect of this formulation on sleep.

Sleep disturbance is highly prevalent and impacted by many interdependent variables. We will examine self-reported sleep disturbance in a broad age-range of adults who have chosen to use this product. The study will incorporate participant reported outcome questionnaires, daily surveys, and the participants' personal health tracking wearable device (e.g. Apple Watch, Fitbit, Smartwatch, etc.) to engage the participant in their sleep health and explore objective digital outcome measures of sleep. An important feature of this consumer-driven study design is to help individual consumers observe the effects of this product on their own sleep patterns during the study itself. There is no "doctor-patient" relationship as part of this research since the participant as a consumer is making the informed choice to take the product and take part in the observational process with self-reported measures. Findings from this study will contribute knowledge toward the design of future sleep research studies, the improvement of the Sip2Sleep® product formulation, and may help inform clinical recommendations for adults interested in using alternative products for sleep.

The following self-reporting measures are used in order to evaluate the effect of Sip2Sleep® in adults with self-reported sleep disturbance:

Surveys to reflect sleep quality, sleep latency, total sleep duration and level of alertness during the day to be distributed daily. Sleep quality and level of alertness during the day will be evaluated with a single 10-point visual analogue scale (VAS) and objective sleep data reflecting sleep latency and total sleep duration will be collected from personal wearable devices.

Insomnia Sleep Index (ISI) is a brief self-report instrument measuring the patient's perception of both nocturnal and diurnal symptoms of insomnia during the past two weeks. The ISI comprises seven items assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item is rated on a five-point scale and the total score indicates the severity of insomnia, with a range of possible scores from 0-28. A score higher than 14 has been indicated to be the optimal cut-off for insomnia as a disorder. The ISI has been widely used in clinical and research settings as it is brief and easy to administer, and can provide valuable information for diagnosis and treatment planning. Research has found that the ISI is sensitive in detecting changes in the patient's perception of treatment outcome, and a good degree of convergence exists between the patient and the clinician's evaluation of insomnia severity.13,14 Generalized Anxiety Disorder-7 (GAD-7) is a self-reported anxiety survey utilized in primary care consisting of a 7-item anxiety scale. The instrument is well supported to use in a general population and normative data can be used to compare a subject's GAD-7 score with those determined from a general population reference group, with evidence of significant reliability and validity with congruent agreement in self-reported and interviewer-administered versions of the scale. GAD and Depression symptoms frequently occur together, but previous studies have supported via factor analysis that this measure can detect GAD and depression as distinct dimensions.15 This measure will be used in combination with other scales to observe self-reported effects on sleep disturbances and insomnia, such as anxiety or other psychiatric disorders.

Inclusion criteria

• Age > 18 years old
• Has self-reported sleep disturbance
• Insomnia Severity Index (ISI) score of > 15 at screening
• Interested in understanding more about the quality of their sleep and chose to use the Sip2Sleep product for sleep
• Willingness to do a minimum of 1 week wash out of current OTC or other products for sleep (e.g. melatonin, anticholinergics)
• Willingness to do a minimum of 1 week wash out of any cannabis products
• Able to receive shipment of the product at an address within the United States If taking prescription hypnotics (e.g. zolpidem, zaleplon, benzodiazepines) or other class of medication for sleep, must be on a stable dose for at least 4 weeks.
• Able to read and understand English
• Able to use a personal smartphone
• Has and is able to use a personal health tracking wearable device (e.g., Apple Watch, Fitbit Smartwatch, Oura Ring, etc.)
• Able to understand and provide informed consent
• Able to complete study assessments over 5 weeks

Exclusion criteria

• Research participants who have no computer, smartphone, and internet access and/or do not use a computer or smartphone
• The following concomitant therapies are excluded:
• Participants taking daily prescription medication for sleep (for example, prescription hypnotics like zolpidem, zaleplon, benzodiazepines) not on a stable dose for at least 4 weeks
• Participants receiving Cognitive Behavioral Therapy for Insomnia (CBTi)
• Participants receiving any investigational therapies or treatments
• Other Illnesses or Conditions: Participants who have the following co-morbidities are excluded:
• Confirmed diagnoses of the following sleep disorders: Narcolepsy, Restless Leg Syndrome, Circadian Rhythm Disorders
• Confirmed diagnosis of Sleep Apnea that is untreated or not well controlled
• Current or prior psychotic disorder
• Current or prior Substance Abuse Disorder
• Current or prior cardiac dysrhythmias (for example, atrial fibrillation, supraventricular tachycardia)
• Currently pregnant, planning to become pregnant in the next 1 month, or breastfeeding
• Allergies or adverse reactions (for example, anxiety) to Montmorency tart cherry extract and/or Venetron®