## Protocol Section
### Identification Module
**NCT ID:** NCT06413810

**Brief Title:** A Randomised, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Effects of a Food Ingredient on Self-reported Stress in Healthy Adults

**Official Title:** A Randomised, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Effects of a Food Ingredient on Self-reported Stress in Healthy Adults

#### Organization Study ID Info
**ID:** AFCRO-177
#### Organization
**Class:** INDUSTRY
**Full Name:** Unilever R&D
### Status Module
#### Completion Date
**Date:** 2024-10

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Atlantia Food Clinical Trials

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Unilever R&D

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of this study is to investigate if a food ingredient can improve stress in healthy adults who experience moderate symptoms of self-reported stress. The main question it aims to answer is if 4 weeks of daily intake of the ingredient reduces stress compared to 4 weeks of daily intake of a placebo product.

Participants will:

* consume both the test and placebo products for 4-weeks each in a randomised order, with 4 weeks in between
* visit the test site 6 times over the 13 weeks
* complete a series of assessments on stress and sleep quality and provide blood, stool and saliva samples

**Detailed Description:** A double-blind, randomised, placebo-controlled, crossover study with 6 visits over 13-weeks. Participants will consume study product or placebo for two 4-week intervention periods.

Primary Objective: To evaluate in healthy adults, experiencing moderate symptoms of self-reported stress, the effect of 4-week daily supplementation of a food ingredient versus placebo on stress.

Secondary Objectives: To evaluate in healthy adults, experiencing moderate symptoms of self-reported stress, the effect of 4-week daily supplementation of a food ingredient versus placebo on:

* Mood
* Plasma GABA levels
* Salivary cortisol awakening response (CAR)
* Acute effects on stress
* Faecal GABA

### Conditions Module

**Conditions:**

- Stress

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 49

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Other: Calmarell

**Label:** Food ingredient

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Other: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Food ingredient

**Description:** Food ingredient

**Name:** Calmarell

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Blinded placebo

**Name:** Placebo

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Measure:** Change in Perceived Stress Scale (PSS) Total Score from baseline to end of intervention

**Time Frame:** 4 weeks

#### Secondary Outcomes

**Measure:** Profile of Mood States Questionnaire (POMS)

**Time Frame:** 4 weeks

**Measure:** Plasma GABA levels

**Time Frame:** 4 weeks

**Measure:** Salivary cortisol awakening response

**Time Frame:** 4 weeks

**Measure:** VAS scale on acute effects on stress

**Time Frame:** 30 hours

**Measure:** Faecal GABA

**Time Frame:** 4 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* To be eligible for inclusion, the Participant must fulfil all the following criteria:

  1. Be able to give written informed consent.
  2. Be between 18 and 50 years of age.
  3. Has a BMI between ≥ 18.0 and ≤ 30.0 kg/m2.
  4. Have moderate stress, as measured on Cohen's Perceived Stress Scale (PSS), with a score between 14 and 26 (inclusive) at both Screening and Baseline Visits.
  5. Is in general good health, as determined by the investigator.
  6. Willing to consume the Study Product daily for the duration of the study and comply with the study procedures.

Exclusion Criteria:

* The presence of any of the following criteria will exclude the Participant from participating in the study:

  1. Scores ≥10 on General Anxiety Disorder 7 item (GAD-7) questionnaire.
  2. Scores ≥10 Patient Health Questionnaire 9 item (PHQ-9).
  3. Participants who are pregnant or wish to become pregnant during the study.
  4. Participants who are lactating and/or currently breastfeeding.
  5. Participants currently of biological childbearing potential, but not using a continuous effective method of contraception, as outlined below:

     1. Complete abstinence from intercourse two weeks prior to administration of the study product, throughout the human study, until the completion of follow-up procedures or for two weeks following discontinuation of the study product in cases where Participant discontinues the study prematurely. (Participants utilising this method must agree to use an alternate method of contraception if they should become sexually active and will be queried on whether they have been abstinent in the preceding two weeks when they present to the clinic for the final visit).
     2. Has a male sexual partner who is surgically sterilised prior to the Screening Visit and is the only male sexual partner for that Participant.
     3. Sexual partner(s) is/are exclusively female.
     4. Use of acceptable method of contraception, such as a spermicide, mechanical barrier (e.g., male condom, female diaphragm), tubal ligation, or contraceptive pill. The Participant must be using this method for at least one week prior to and one week following the end of the study.
     5. Use of any intrauterine device (IUD) or contraceptive implant. The Participant must have the device inserted at least two weeks prior to the first screening visit, throughout the study, and two weeks following the end of the study.
  6. Is hypersensitive to any of the components of the Study Product.
  7. Have a significant acute or chronic coexisting illness such as such as uncontrolled hypertension, type 1 or 2 diabetes, cardiovascular diseases or any condition which may, in the opinion of the investigator, impact their ability to participate in the study or impact the study outcomes.
  8. Use of systemic antibiotics within the 12 weeks prior to Visit 1.
  9. Use of systemic immunosuppressant drugs, steroids, etc. within the 12 weeks prior to Visit 1.
  10. Participants diagnosed and treated with prescribed medications for anxiety and depression in the 12 weeks prior to Visit 1.
  11. Participants who have taken 3 doses laxative or anti-diarrheal medication in the past 12 weeks, at investigator discretion.
  12. Herbal treatments for mood disorders or psychological conditions (e.g., valerian, St. John's Wort) within 4 weeks prior to Visit 1 or planning to start during the study period.
  13. Disease such as coeliac disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, diverticulosis, stomach or duodenal ulcers, gastroesophageal reflux disease (GERD) that by the investigator's judgement, could interfere with the intestinal barrier function or have undergone significant gastrointestinal surgery (appendectomy and cholecystectomy acceptable).
  14. Participants consuming prebiotics (containing fructans, galacto-oligosaccharides, psyllium husk, inulin as main component), or probiotics within last 4 weeks prior to Visit 1.
  15. Participants consuming GABA or glutamate supplements, or any other supplements that are thought to directly affect digestive health and mental well-being within 4 weeks prior to Visit 1 which in the opinion of the investigator, impact the study outcomes.
  16. Participants with a current history of drug (including illicit drug) and /or alcohol abuse at the time of enrolment.
  17. Has received treatment involving experimental supplements in the past 4 weeks, at the discretion of the investigator.
  18. Major changes in lifestyle (i.e., diet, dieting, exercise level, travelling, supplements) for duration of the study.
  19. Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the study.
  20. Any Participant who is an employee of the study site or an Atlantia Clinical Trials employee or their immediate family member or a member of their household.

**Healthy Volunteers:** True

**Maximum Age:** 50 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** amelia.jarman@unilever.com

**Name:** Amelia C Jarman, PhD

**Phone:** +447776490919

**Role:** CONTACT

**Contact 2:**

**Email:** simone.pyle@unilever.com

**Name:** Simone Pyle, PhD

**Phone:** +447999544694

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Cork

**Contacts:**

***Contact 1:***

- **Email:** egoodbody@atlantiatrials.com

- **Name:** Emily Goodbody

- **Phone:** +353 (0) 86-218-8787

- **Role:** CONTACT

***Contact 2:***

- **Email:** lvaz@atlantiatrials.com

- **Name:** Lavita Vaz

- **Phone:** +353 (0) 021-430-7442

- **Role:** CONTACT

***Contact 3:***

- **Name:** Timothy Dinan, Prof

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Ireland

**Facility:** Atlantia Clinical Trials

**State:** Co Cork

**Zip:** T23 R50R

#### Overall Officials

**Official 1:**

**Affiliation:** Atlantia Clinical Trials

**Name:** Timothy Dinan, Prof

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Misc Info Module

- Version Holder: 2024-05-31
