Clinical trial NCT06789718: Impact of GABA Probiotic Lactiplantibacillus Plantarum Lp815 on Sleep Outcomes in Participants with Self-Reported Sleep Disturbance
Official title: A Direct-to-Consumer, Randomized, Double-blind, Placebo-controlled Study Assessing the Impact of GABA Probiotic Lactiplantibacillus Plantarum Lp815 on Sleep Outcomes in Participants with Self-Reported Sleep Disturbance
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Insomnia (moderate)
Lead sponsor: Verb Biotics LLC
Sponsor class: INDUSTRY
First posted: 2025-01-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Generally healthy participants (all genders) 18 years or older who have self-reported sleep disturbance with a score of \>15 on the screening Insomnia Severity Index questionnaire.

Brief summary: The rationale for this study is to observe differences in sleep outcomes between a consumer-grade probiotic capsule called GABA Probiotic and a placebo control group. Additionally, the study aims to evaluate the impact of the probiotic product on anxiety, gastrointestinal symptoms, sleep quality, daytime alertness, mood, stress, severity of night sweats (if present), and quality of life. In a subset of participants, the study also aims to evaluate how the probiotic affects neurotransmitter levels in the body using an at-home urinary test. A consumer-driven, decentralized observational clinical research study is therefore well-suited for evaluating the impact of this probiotic product in this population.

Detailed description: Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the human nervous system, helping to slow down the stimulation of nerve signals in the brain. GABA plays a pivotal role in calming anxiety, reducing stress and improving sleep. Deficits in GABA levels can lead to a cascade of disorders ranging from anxiety and stress to mood swings and depression. Advancements in understanding the role of the microbiome in the Gut-Brain Axis have highlighted its untapped potential in regulating mood, stress, and sleep via neurotransmitter production.

Several bacterial strains, including lactic acid bacteria, bifidobacteria and others, have demonstrated GABA production capabilities. However, the magnitude of GABA output varies among these strains, and their efficacy in GABA synthesis within the human gastrointestinal environment is uncertain. This stems from the fact that GABA synthesis, typically a pH-stress response, stalls in less acidic environments.

Lactiplantibacillus plantarum Lp815 stands out. Using advanced computational and high-throughput screening techniques, we identified this strain's superior GABA production capability. Remarkably, it synthesizes a significant amount of GABA within the physiologically relevant pH range.

The study will evaluate self-reported sleep disturbance in a broad age-range of adults who have chosen to try this product. The study will incorporate participant reported outcome questionnaires and surveys, the use of a health tracking wearable device to explore objective digital outcome measures of sleep, heart rate and heart rate variability and in a subset of participants, the study will utilize an at-home urinary test to evaluate neurotransmitter levels in the body. 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 and a simple urine test that can be done at home. Findings from this study will contribute knowledge toward the dosing and formulation of the probiotic product and the design of future studies.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Has self-reported sleep disturbance
* Insomnia Severity Index (ISI) score of \> 15, with score on question on difficulty falling asleep \> 2 ("moderate") at screening
* Interested in understanding more about their sleep and choose to use the probiotic product
* Willing to do a 1-week washout out of any OTC or other products for sleep and/or (e.g. melatonin, anticholinergics, valerian root etc.) prior to randomization and refrain from use for the duration of the study
* Willing to do a 4-week washout from any systemic antibiotic, prebiotic, probiotic and postbiotic use prior to randomization
* If taking prescription medications for sleep and/or anxiety (e.g. Benzodiazepines, zolpidem, zaleplon, SSRIs, Buspirone, Tricyclics, MAOIs), or other class of medication for sleep, must be on a "stable dose" for at least 4 weeks prior to randomization. "Stable dose" is defined as no changes in dosage or frequency of the specified medications for at least 4 weeks prior to randomization and throughout the study period.
* If using any cannabis-containing products, must be on a stable dose for at least 4 weeks prior to randomization and consume \< 10 mg/day of THC
* If regularly consuming alcohol, must be willing to stay on a stable amount throughout the study period and to log alcohol consumption.
* In good general health at the time of screening (Investigator discretion).
* Able to read and understand English.
* Able to read, understand, and provide informed consent.
* Able to use a personal smartphone device and download Chloe by People Science.
* Able to receive shipment of the product at an address within the United States.
* Is willing to wear, sync daily, and charge twice weekly a provisioned health tracking wearable device (Oura ring) everyday (up to 7 weeks) during sleep. If the participant already has an Oura ring, they can use their own device and account.
* Able to complete study assessments over the course of up to 7 weeks.

Exclusion Criteria:

* Do not have a smartphone and/or internet access.
* Concomitant Therapies:

  * Participants taking prescription medication for sleep and/or anxiety (e.g. Benzodiazepines, zolpidem, zaleplon, SSRIs, Buspirone, Tricyclics, MAOIs) 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 within 30 days prior to randomization.
  * Participants taking any other prescription medications that impact systemic GABA levels (e.g., GABA supplements, barbiturates, gabapentin, pregabalin, valproate, tiagabine, vigabatrin, baclofen)
  * Participants currently taking or have taken probiotics, prebiotics or postbiotics within the past 4 weeks prior to randomization.
  * Current antibiotic use or use within 4 weeks prior to randomization.
* Other Illnesses or Conditions: Participants who have the following conditions or comorbidities 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
  * Known diagnosis of Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis) or Irritable Bowel Syndrome
  * Current or prior history of psychotic disorder
  * Confirmed diagnosis of major depressive disorder or bipolar disorder
  * Diagnosed with Alcohol or Substance Abuse Disorder
  * Currently pregnant, planning to become pregnant in the next 1 month, or breastfeeding
  * Presence of any infection or illness that causes chronic night-waking or impairs ability to retain urine overnight (e.g., chronic pain, uncontrolled benign prostatic hyperplasia, prostatitis, urinary tract infection, catheterization, etc.).
  * Have a significant illness, disease or condition which, in the opinion of the principal investigator, may impact their ability to participate in the trial or impact the trial outcomes.
* Known hypersensitivity or previous allergic reaction to microcrystalline cellulose (MCC).
* Presence of another environmental factor that severely impacts sleep quality (e.g., a new baby, pet or other loved one that wakes frequently or needs frequent care or feeding throughout the night)
* Work in an environment requiring shift work (e.g., rotating shifts, night shifts, or irregular hours).
* Have any known and planned international travel during the study period.
* Are unlikely for any reason to be able to comply with the trial or considered unsuited for participation in the study by the Principal Investigator.

Primary outcomes:
measure: Observe differences in sleep outcomes
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
Secondary outcomes:
measure: Evaluate the impact of GABA Probiotic on anxiety
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
measure: Evaluate the impact of GABA Probiotic on gastrointestinal symptoms
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
measure: Evaluate the impact of GABA Probiotic on subjective sleep quality
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
measure: Evaluate the impact of GABA Probiotic on daytime alertness
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
measure: Evaluate the impact of GABA Probiotic on mood
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
measure: Evaluate the impact of GABA Probiotic on night sweats
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
measure: Evaluate the impact of GABA Probiotic on quality of life
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
measure: Evaluate the impact of GABA Probiotic on improvement in sleep
timeFrame: Participants will complete up to a 16-week study consisting of screening period, randomization and shipping period, a baseline period, and a 6-week product/placebo use period.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: People Science, Inc.
state: California
Study officials:
affiliation: People Science, Inc.
name: Noah Craft, MD
role: PRINCIPAL_INVESTIGATOR
References: