AN OPEN-LABEL, ACUTE CLINICAL TRIAL TO ASSESS THE LEVEL OF KETONE PRODUCTION FOLLOWING CONSUMPTION OF AVELA™ (R)-1,3-BUTANEDIOL IN AN ADULT POPULATION

Study Overview
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Brief Summary
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The purpose of the pilot clinical trial described herein is to determine the level of ketone production [measured as β hydroxybutyrate (BHB)] following consumption of (R)-1,3-butanediol in a beverage and to record gastrointestinal (GI) symptomology, as well as any effects on alertness/sleepiness.

Detailed Description
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Primary: To evaluate the level of production of BHB following the consumption of 3 servings of Avela™, with consumption of each serving separated by 30 minutes and each serving providing 11.5 g of (R)-1,3-butanediol [total intake of 34.5 g of (R)-1,3-butanediol]. BHB levels will be measured using capillary whole blood from the fingertips using at home Keto-Mojo monitoring system (β-Ketone, as beta-hydroxybutyrate, in fingertip capillary whole blood). Measurement Range: 0.1 - 8.0 mmol/L Measurement time (min): 0, 30, 60, 90, 120, 180, 240, 300 Secondary: To evaluate the acute effects of 3 servings of Avela™, with consumption of each serving separated by 30 minutes and each serving providing 11.5 g of (R)-1,3-butanediol [i.e., total intake of 34.5 g (R)-1,3-butanediol] on: GI tolerance. All subjects will complete the mVAS GI symptoms tool at baseline (0 minutes), and at 30, 60, 90, 120, 180, 240, and 300 minutes. A validated tool to measure GI tolerability of (R)-1,3-butanediol will be utilized. The mVAS GI symptoms tool is a self-administered questionnaire, which is modeled after the validated gold standard measurement tool predominantly used to test clinical gastroenterology scenarios (Bengtsson et al., 2013). Sleepiness/alertness The SSS (Shahid et al., 2012) is a subjective tool to assess how alert a subject is feeling at specific moments in time. The scale requires respondents to select a rating of 1 to 7, where a 1 indicates the subject is feeling active, vital, alert, or wide awake and the highest score of 7 indicates the subject is no longer fighting sleep, sleep onset soon; having dream-like thoughts (Hoddes et al., 1973). The scale is validated, correlating r = 0.68 with performance on the Wilkinson tests. All subjects will complete the SSS at baseline (0 minutes) and at 30, 60, 90, 120, 180, 240, and 300 minutes.

Official Title
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AN OPEN-LABEL, ACUTE CLINICAL TRIAL TO ASSESS THE LEVEL OF KETONE PRODUCTION FOLLOWING CONSUMPTION OF AVELA™ (R)-1,3-BUTANEDIOL IN AN ADULT POPULATION

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: (R)-1,3-butanediol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 18 to 65 years of age BMI 18 to <35.0 kg/m2, inclusive Weight ≥ 110 lbs Subject is judged to be in good health on the basis of medical history Subject is willing to fast for 12 hours prior to study start Subject is willing to avoid alcohol and intense physical activity the day prior to and on the day of testing Subject is capable of giving informed consent and complying with all study procedures/requirements. Exclusion Criteria: Previous GI disorders (e.g., inflammatory bowel disease, irritable bowel syndrome, history of surgery for weight loss, or gastroparesis) Gastroenteritis in the 2 weeks preceding the study Diabetes Weight <110 lbs History of alcohol or drug abuse Previous diagnosis of neurological disorders, depression, or mental illness with psychosis Unexplained alarm features (i.e., unintentional weight loss >10% body weight in the last 3 months, fevers, or blood in stools) Use of an antibiotic or any medication impacting gut transit during the 2 weeks before the study Constipation or diarrhea (defined as, on average, less than 3 stools per week or more than 3 stools per day, respectively) Allergy to tree nuts Women who are pregnant or breastfeeding Persons with medical conditions affecting the pancreas, liver, thyroid, or gall bladder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avela™ (R)-1,3-Butanediol<br>3 servings of Avela™, with consumption of each serving separated by 30 minutes and each serving providing 11.5 g of (R)-1,3-butanediol [total intake of 34.5 g of (R)-1,3-butanediol]. | Dietary Supplement: (R)-1,3-butanediol<br>* Avela™ (R)-1,3-butanediol is intended to induce ketosis in the general adult population. Avela™ (R)-1,3-butanediol is GRAS for use in beverages, bars, and gels<br>* Other names: Avela;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the level of production of BHB measure of blood ketones levels (i.e., blood BHB levels) | β-Ketone, as beta-hydroxybutyrate, in fingertip capillary whole blood, Measurement Range: 0.1 - 8.0 mmol/L | 0, 30, 60, 90, 120, 180, 240, and 300 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess GI symptomology | Modified visual analogue scale (mVAS) GI symptoms tool | 0, 30, 60, 90, 120, 180, 240, and 300 minutes | 
| To assess Sleepiness/alertness | Stanford Sleepiness Scale (SSS) | 0, 30, 60, 90, 120, 180, 240, and 300 minutes |