Impact of Levagen+® Palmitoylethanolamide (PEA) in a Cross-Over Trial Examining Stress and Cognition in University Students (IMPRESS)

The Effect of Levagen+® Palmitoylethanolamide (PEA) Supplementation on Parameters of Stress, Wellbeing and Cognition in University Students

The goal of this randomised cross-over trial is to learn about the effects of Levagen+® Palmitoylethanolamide (PEA) supplementation on cognition, wellness and well-being in young and healthy university students.

The main question it aims to answer is:

• Does the PEA supplementation affect parameters of stress, mood, cognition and well-being in university students?

Participants will complete 2 baseline on-site visits during which they will be assigned to Levagen+® Palmitoylethanolamide (PEA) treatment or placebo arm each time and:

• complete anthropometric measurements, questionnaires and surveys,
• undergo blood and saliva sampling
• complete a cognitive assessment (CANTAB)
• a randomly chosen cohort will also measure heart rate variability (HRV) over 3 days.

Researchers will compare the PEA treatment group to the placebo to see if there is a significant difference.

Study Overview

• Status: Active, not recruiting
• Conditions: Wellness, Psychological; Well-Being, Psychological
• Intervention / Treatment: Dietary supplement: Levagen+® Palmitoylethanolamide (PEA); Dietary supplement: Placebo

Detailed Description

The study will investigate the effect of Levagen+® Palmitoylethanolamide (PEA) supplementation on parameters of stress, well-being and cognition at defined time points. Assessments will be made using a combination of a range of stress measures, which will include physiological and psychometric parameters.

Physiological measures will include assessments of known biomarkers of the principal stress-sensitive physiological systems, the hypothalamic-pituitary-adrenal axis, and the autonomic nervous system, while psychometric measures will include established instruments to assess general health, somatic stress symptoms, academic stress, response to stress, cognition, and mood.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W1W 6UW
    • University of Westminster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males & Females
• 18 to 40 years of age
• Fully enrolled full-time university students from London

Exclusion Criteria:

• Consumption of >14 servings of alcohol/week
• Any learning disability (e.g. dysphasia)
• Any neurobiological disorders (e.g. autism)
• Smokers Any allergies/health issues related to items being ingested
• Any serious illnesses or those on chronic medication
• Any pregnant or lactating women
• Any woman who is trying to conceive
• Any chronic gastrointestinal disorders
• Any chronic menstrual disorders (e.g. PCOS)
• Any subjects who have undergone menopause or undergoing the perimenopause transition
• Any eating disorders
• Any depression/mental disorders
• Any obese sedentary (not physically active) individual, according to BMI values
• Any abnormal blood pressure levels
• Shift work

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Levagen+® Palmitoylethanolamide (PEA); Levagen+® Palmitoylethanolamide (PEA) - 700mg/day, containing not less than 600 mg PEA.	Dietary supplement: Levagen+® Palmitoylethanolamide (PEA); Participants were instructed to swallow 2 opaque capsules (Levagen+® - 90% of PEA) with water daily at the same time of the day for 6 weeks.
Placebo Comparator: Placebo; Placebo - Microcrystalline Cellulose	Dietary supplement: Placebo; Participants were instructed to swallow 2 opaque capsules (Microcrystalline Cellulose) with water daily at the same time of the day for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the influence of PEA supplementation on the perceived difficulties of test execution.	Motor Screening Task (MOT) was used as a screening tool to indicate difficulties in test execution as part of the Core Cognition battery - CANTAB by Cambridge Cognition.	The parameters were measured during the baseline visit (day 1) and during the endpoint visit (day 42) of the 6-week supplementation period.
To assess the influence of PEA supplementation on the reaction and movement speed and attention.	Reaction Time (RTI) was used to measure reaction and movement speed and attention as part of the Core Cognition battery - CANTAB by Cambridge Cognition.	The parameters were measured during the baseline visit (day 1) and during the endpoint visit (day 42) of the 6-week supplementation period.
To assess the influence of PEA supplementation on visual and episodic memory and visuospatial associative learning.	Paired Associated Learning (PAL) was used to measure visual and episodic memory and visuospatial associative learning as part of the Core Cognition battery - CANTAB by Cambridge Cognition.	The parameters were measured during the baseline visit (day 1) and during the endpoint visit (day 42) of the 6-week supplementation period.
To assess the influence of PEA supplementation on short-term and spatial working memory and problem solving.	Spatial Working Memory (SWM) was used to measure short-term and spatial working memory and problem solving as part of the Core Cognition battery - CANTAB by Cambridge Cognition.	The parameters were measured during the baseline visit (day 1) and during the endpoint visit (day 42) of the 6-week supplementation period.
To assess the influence of PEA supplementation on visual processing, recognition, and sustained attention.	Rapid Visual Information Processing (RVP) was used to assess visual processing, recognition, and sustained attention as part of the Core Cognition battery - CANTAB by Cambridge Cognition.	The parameters were measured during the baseline visit (day 1) and during the endpoint visit (day 42) of the 6-week supplementation period.
To assess the influence of PEA supplementation on Serum Brain-derived neurotrophic factor (BDNF) levels.	Serum BDNF levels were measured.	The parameters were measured at the baseline visit (day 1) and at the endpoint visit (day 42) of the 6-week supplementation period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the influence of PEA supplementation on HRV in female population.	HRV was measured for 3 full days.	The parameters were measured for 3 continuous days following the baseline visit (day 1, day 2 and day 3) and for 3 continuous days following the endpoint visit (day 42, day 43 and day 44) of the study period.
To study the influence of PEA supplementation on the degree of perceived stress in females.	The Perceived Stress Scale (PSS) a 10-item questionnaire was used to measure the degree to which situations in the participant's life were appraised as stressful. The questions investigate how often certain feelings and thoughts were experienced on a five-point scale from 'never' to 'very often' (never =0, almost never = 1, sometimes = 2, fairly often = 3 and very often = 4) during the 3-day observation periods. To calculate a total PSS score, responses to the four positively stated items (items 4, 5, 7 and 8) first need to be reversed (i.e. 0 => 4; 1 => 3; 2 => 2; 3 => 1; 4 => 0). The PSS score were then obtained by summing across all items. Higher scores indicate higher levels of perceived stress.	The parameters were measured for 3 continuous days following the baseline visit (day 1, day 2 and day 3) and for 3 continuous days following the endpoint visit (day 42, day 43 and day 44) of the study period.
To study the influence of PEA supplementation on perceived emotions in females.	The Positive and Negative Affect Schedule (PANAS) was used to assess feelings of both positive and negative emotions experienced simultaneously.	The parameters were measured for 3 continuous days following the baseline visit (day 1, day 2 and day 3) and for 3 continuous days following the endpoint visit (day 42, day 43 and day 44) of the study period.
To study the influence of PEA supplementation on well-being in females.	Student Well-being Process Questionnaire (WPQ) a 44-item questionnaire was used to examine predictors of positive well-being, adverse mental health, and cognitive function. The responses to questions 1 - 42 were assessed on a 10-point scale and or questions 43 and 44 on a 4-point scale. Where with outcomes related to positive well-being high scores = more positive; with outcomes related to adverse mental health high scores = more negative and with outcomes related to cognitive function high scores = more cognitive problems. Positive well-being was predicted by high positive personality, high social support and low stressor and low negative coping scores. Negative outcomes were predicted by high stressor, coping and conscientiousness scores, and low positive personality and low social support scores. Cognitive problems were predicted by high stressor and negative coping scores and low positive personality scores.	The parameters were measured for 3 continuous days following the baseline visit (day 1, day 2 and day 3) and for 3 continuous days following the endpoint visit (day 42, day 43 and day 44) of the study period.
To assess the influence of PEA supplementation on parameters of inflammation.	Interferon-gamma (pg/mL), Interleukin-1 beta (pg/mL), Interleukin 6 (pg/mL), Interleukin 10 (pg/mL), Tumour necrosis factor alpha (pg/mL) levels were measured.	The parameters were measured at the baseline visit (day 1) and at the endpoint visit (day 42) of the 6-week supplementation period.
To assess the influence of PEA supplementation on Salivary Cortisol	Salivary Cortisol levels were measured during morning, afternoon and evening for 3 days following each baseline and endpoint visit at home.	The parameters were measured in morning and afternoon samples collected over 3 continuous days following the baseline visit (day 1, day 2 and day 3) and 3 continuous days following the endpoint visit (day 42, day 43 and day 44) of the study period.

Collaborators and Investigators

• Sponsor: University of Westminster
• Collaborators: Gencor Pacific Group
• Investigators: Principal Investigator: Mohammed Gulrez Zariwala, PhD, University of Westminster; Principal Investigator: Sanjoy Deb, PhD, Anglia Ruskin University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: January 3, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Actual): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: cognition; stress; well-being; inflammation; BDNF; supplement; wellness; palmitoylethanolamide; nutraceutical; PEA
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Palmidrol
• Other Study ID Numbers: ETH2122-1031

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No