Probiotics for Enhanced Tissue Carotenoid Status in Premenopausal Women

Gut Microbiome Clinical Trial

— ProCar  

Official title:

Probiotics for Enhanced Tissue Carotenoid Status: a Double-blind, Randomized, Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04511052
• Other study ID #: A12-M57-19B
• Secondary ID: IT15250
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 1, 2021
• Est. completion date: September 13, 2022

Study information

• Verified date: November 2023
• Source: McGill University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Carotenoids are yellow-orange fat soluble plant pigments primarily obtained from the diet that serve as an accurate biomarker for fruit and vegetable intake. Carotenoids have demonstrated antioxidant, anti-inflammatory, and anti-obesogenic properties among others. Excess carotenoids are deposited in the skin for storage where they protect against UV skin damage and contribute to improvements in skin health (i.e., decrease the appearance of wrinkles). However, carotenoid status is linked to bioavailability and absorption, which has a high inter-individual variability. It has been hypothesized that inter-individual variations are related to the diversity of gut microbiota. The aim of the present study is to determine whether probiotic supplementation can enhance carotenoid status and responsiveness to carotenoid-mediated changes in blood and skin from intake of a supplement containing mixed forms of carotenoids in pre-menopausal women.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: September 13, 2022
• Est. primary completion date: September 13, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 30 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Healthy non-menopausal or non-perimenopausal women,

2. 30-50 years of age,

3. BMI of 18.5 - 29.9 kg/m2,

4. Access to a smartphone that has a camera and iOS 11.0 or Android 4.2 and up,

5. Visible fine to moderate wrinkles on the face (e.g. forehead, crow's feet area, etc.),

6. Fitzpatrick scale of types I, II, & III

7. Urine pregnancy test of negative

8. Willing to maintain current physical activity and dietary habits

9. Willing to refrain from taking natural health products containing carotenoids (beta-carotene, lutein, lycopene, etc.)

10. Willing to discontinue consumption of probiotic supplements and food containing added probiotics (e.g. yogurts with live, active cultures or supplements) or fermented foods (e.g. Kefir, pickles, etc.) upon screening and for the duration of the study,

11. Willing to apply the moisturizer provided on every day throughout the study upon admission to the study (about -2 weeks),

12. Willing to refrain from using any cream (including the moisturizer provided) and makeup on the face for study visits and photo capture (face, eyes and lips),

13. Able to understand and comply with requirements of the study (e.g. complete all clinical visits, questionnaires, records, and diaries),

14. Able to provide a written informed consent.

Exclusion Criteria:

1. Known immunodeficiency (immuno-compromised and immuno-suppressed participant; e.g. AIDS, lymphoma, participants undergoing long-term corticosteroid treatment, chemotherapy and allograft participant),

2. Known chronic or acute illness (e.g. hepatitis, diabetes, high blood pressure, jaundice, etc.), unless under control via medication,

3. History of illness or use of any type of drug that may interfere with the investigational product or intervention (e.g. antibiotics) within 1 month of screening (may be eligible to participate after a 2-week washout period),

4. Known chronic or acute skin condition on the face (e.g. eczema, psoriasis, severe acne, rosacea, etc.),

5. Facial surgery (e.g. lifting, facial rejuvenation) or chemical treatment (e.g. Botox injection) within 5 years before study start,

6. Frequent tanning salons, use tanning products, or foresee high exposure to the sun during the study,

7. Tattoos on the face or palms of the hands,

8. Milk, soy or yeast allergy,

9. Routine use of dietary supplements that may interfere with outcomes measured (e.g. anti-oxidant, anti-inflammatory, herbal),

10. Use of probiotic products in the past 2 weeks (may be eligible to participate after a 2-week washout period),

11. Allergy to any of the ingredients contained in the moisturizer provided,

12. Use of antiaging creams containing retinol, glycolic acid, Coenzyme Q, etc. (may be eligible to participate after a 2 weeks washout period upon admission to the study),

13. Current smoker (tobacco or cannabis),

14. Excessive alcohol consumption (>1 drink/day),

15. Drug abuse or addiction,

16. Bleeding/blood disorder

17. Psychological disorder

18. Currently enrolled in another trial

19. Positive pregnancy test in women of child-bearing potential; breast-feeding or planning on becoming pregnant during the course of the study (determined by a pregnancy test performed at the screening visit),

20. Women of child-bearing potential not using effective contraception which include:

• Hormonal contraceptives including combined oral contraceptives, hormone birth control patch, vaginal contraceptive ring, injectable contraceptives, or hormonal implants
• Intrauterine devices (IUD) or Intrauterine system (IUS)
• Tubal ligation
• Vasectomy of partner
• Barrier method (condom or occlusive cap with spermicide)
• Abstinence

21. Participation in a similar study within 3 months of the screening visit.

Related Conditions & MeSH terms

• Carotenoid Status
• Gut Microbiome
• Skin Health

Intervention

Dietary Supplement:
• Probiotic
Daily intake of 10 x 10^9 CFU of a proprietary strain for a total duration of 10 weeks

Other:
• Placebo
1 capsule daily containing the same carrier material that is similar in size, shape and taste to the probiotic, for a duration of 10 weeks

Dietary Supplement:
• Carotenoid supplement
1 capsule daily containing ~20 mg of total carotenoids for a total duration of 10 weeks

Locations

Country	Name	City	State
Canada	Mary Emily Clinical Nutrition Research Unit (7 rue maple)	Sainte-Anne-de-Bellevue	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
McGill University	Lallemand Health Solutions

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in skin yellow color saturation measured by a spectrophotometer	Average b* value (yellow coloration designated by the CIELab color space) measured from the palm and forehead by spectrophotometry	Week 0, 5, and 10
Secondary	Changes in blood plasma carotenoid status	Blood plasma HPLC or LC-MS analysis	Week 0, 5, and 10
Secondary	Changes in yellow skin color saturation measured by image analysis	Average b* value (yellow coloration designated by the CIELab color space) measured by image analysis of the palm and forehead	Week 0, 5, and 10
Secondary	Changes in fecal microbial composition	16s rRNA sequencing	Week -2, 0, 5, and 10
Secondary	Changes in recovery of probiotic strain	16s rRNA qPCR	Week -2, 0, 5, and 10
Secondary	Changes in skin hydration	Measured using a Courage + Khazaka probe system	Week 0, 5, and 10
Secondary	Changes in skin elasticity	Measured using the Tewameter probe from Courage + Khazaka probe system	Week 0, 5, and 10
Secondary	Changes in skin trans-epidermal water loss	Measured using a Courage + Khazaka probe system	Week 0, 5, and 10
Secondary	Changes in facial skin wrinkling	Images of participants will be individually rated by two trained specialists based on the skin aging atlas 1 - Caucasian type book at four different regions: forehead, crow's feet, nasolabial fold, and upper lip	Week 0, 5, and 10
Secondary	Changes in plasma interleukin 1ß (IL-1ß) levels	Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay.	Week 0, 5, and 10
Secondary	Changes in plasma interleukin-6 (IL-6) levels	Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay.	Week 0, 5, and 10
Secondary	Changes in plasma interleukin-8 (IL-8) levels	Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay	Week 0, 5, and 10
Secondary	Changes in plasma tumor necrosis factor- a (TNF-a) levels	Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay.	Week 0, 5, and 10
Secondary	Changes in plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels	Assessed via LC-MS	Week 0, 5, and 10
Secondary	Changes in plasma F-2 isoprostane levels	Assessed via LC-MS	Week 0, 5, and 10
Secondary	Changes in plasma progesterone levels	Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel	Week 0, 5, and 10
Secondary	Changes in plasma estradiol levels	Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel	Week 0, 5, and 10
Secondary	Changes in plasma testosterone levels	Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel	Week 0, 5, and 10
Secondary	Changes in plasma cortisol levels	Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel	Week 0, 5, and 10
Secondary	Changes in plasma cholesterol levels	Using a colorimetric assay	Week 0, 5, and 10
Secondary	Changes in plasma antioxidant capacity	Measured using the 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assay	Week 0, 5, and 10
Secondary	Changes in Vitamin A status	Plasma HPLC analysis	Week 0, 5, and 10
Secondary	Changes in perceived health and attractiveness	A perception trial is a validated method used to determine the attractiveness preferences of participants (Lefevre & Perrett, 2015). Images of participants from the intervention trial will be sent to the Department of Psychology at McGill University, where the laboratory coordinator will set up an electronic survey that will display randomized sets of images from the same intervention participant at all timepoints (week 0, 5, and 10) of the intervention, in randomized order of presentation (left and right). A separate group of 60 participants will be recruited to participate in the perception trial and assess the images of the intervention participants. These participants will be trained using a few sample photos and then will be instructed to choose the most attractive and healthy looking face in a forced-choice paradigm for each comparison presented in the electronic survey.	Week 0, 5, and 10
Secondary	Changes in quality of life assessed by SF-36 questionnaire	The short form 36-Item Health Survey 1.0 Questionnaire is a validated questionnaire that will be used to assess QoL as a recent study (Valler-Colomer et al., 2019) demonstrated a consistent association between higher QoL indicators and particular gut microbiota profiles (butyrate-producing Faecalibacterium and Coprococcus bacteria). This survey consists of 36 items that average together to indicate eight scale scores for various health indicators (e.g., emotional well-being, general health, etc.). Scores range from 0-100, with higher scores representing better health. Carotenoid supplementation has also demonstrated improvements in sub-optimal symptoms of physical and emotional health measured via various self-reported questionnaires (Stringham et al., 2018).	Week 0, 5, and 10