ProCar: Probiotics for Enhanced Tissue Carotenoid Status in Premenopausal Women

Sponsor

McGill University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04511052

Collaborator

Lallemand Health Solutions (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Carotenoid Status Gut Microbiome Skin Health	Dietary Supplement: Probiotic Other: Placebo Dietary Supplement: Carotenoid supplement	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Screening

Official Title:

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

Actual Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carotenoid + Probiotic Carotenoid: 1 capsule daily of a mixed carotenoid (~ 20 mg total carotenoids) supplement Probiotic: 1 capsule daily containing 10 x 10^9 CFU of a proprietary strain Total duration: 10 weeks	Dietary Supplement: Probiotic Daily intake of 10 x 10^9 CFU of a proprietary strain for a total duration of 10 weeks Dietary Supplement: Carotenoid supplement 1 capsule daily containing ~20 mg of total carotenoids for a total duration of 10 weeks
Placebo Comparator: Carotenoid + Placebo Carotenoid: 1 capsule daily of a mixed carotenoid (~ 20 mg total carotenoids) supplement Placebo: 1 capsule daily containing the same carrier material of the probiotic, that is also similar in size, shape, and taste. Total duration: 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

Arm

Intervention/Treatment

Experimental: Carotenoid + Probiotic

Carotenoid: 1 capsule daily of a mixed carotenoid (~ 20 mg total carotenoids) supplement Probiotic: 1 capsule daily containing 10 x 10^9 CFU of a proprietary strain Total duration: 10 weeks

Dietary Supplement: Probiotic

Daily intake of 10 x 10^9 CFU of a proprietary strain for a total duration of 10 weeks

Dietary Supplement: Carotenoid supplement

1 capsule daily containing ~20 mg of total carotenoids for a total duration of 10 weeks

Placebo Comparator: Carotenoid + Placebo

Carotenoid: 1 capsule daily of a mixed carotenoid (~ 20 mg total carotenoids) supplement Placebo: 1 capsule daily containing the same carrier material of the probiotic, that is also similar in size, shape, and taste. Total duration: 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

Outcome Measures

Primary Outcome Measures

Changes in skin yellow color saturation measured by a spectrophotometer [Week 0, 5, and 10]
Average b* value (yellow coloration designated by the CIELab color space) measured from the palm and forehead by spectrophotometry

Secondary Outcome Measures

Changes in blood plasma carotenoid status [Week 0, 5, and 10]
Blood plasma HPLC or LC-MS analysis
Changes in yellow skin color saturation measured by image analysis [Week 0, 5, and 10]
Average b* value (yellow coloration designated by the CIELab color space) measured by image analysis of the palm and forehead
Changes in fecal microbial composition [Week -2, 0, 5, and 10]
16s rRNA sequencing
Changes in recovery of probiotic strain [Week -2, 0, 5, and 10]
16s rRNA qPCR
Changes in skin hydration [Week 0, 5, and 10]
Measured using a Courage + Khazaka probe system
Changes in skin elasticity [Week 0, 5, and 10]
Measured using the Tewameter probe from Courage + Khazaka probe system
Changes in skin trans-epidermal water loss [Week 0, 5, and 10]
Measured using a Courage + Khazaka probe system
Changes in facial skin wrinkling [Week 0, 5, and 10]
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
Changes in plasma interleukin 1β (IL-1β) levels [Week 0, 5, and 10]
Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay.
Changes in plasma interleukin-6 (IL-6) levels [Week 0, 5, and 10]
Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay.
Changes in plasma interleukin-8 (IL-8) levels [Week 0, 5, and 10]
Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay
Changes in plasma tumor necrosis factor- α (TNF-α) levels [Week 0, 5, and 10]
Assessed with MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay.
Changes in plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels [Week 0, 5, and 10]
Assessed via LC-MS
Changes in plasma F-2 isoprostane levels [Week 0, 5, and 10]
Assessed via LC-MS
Changes in plasma progesterone levels [Week 0, 5, and 10]
Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel
Changes in plasma estradiol levels [Week 0, 5, and 10]
Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel
Changes in plasma testosterone levels [Week 0, 5, and 10]
Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel
Changes in plasma cortisol levels [Week 0, 5, and 10]
Analysis using MILLIPLEX MAP Multi-Species Hormone Magnetic Bead Panel
Changes in plasma cholesterol levels [Week 0, 5, and 10]
Using a colorimetric assay
Changes in plasma antioxidant capacity [Week 0, 5, and 10]
Measured using the 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assay
Changes in Vitamin A status [Week 0, 5, and 10]
Plasma HPLC analysis
Changes in perceived health and attractiveness [Week 0, 5, and 10]
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.
Changes in quality of life assessed by SF-36 questionnaire [Week 0, 5, and 10]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy non-menopausal or non-perimenopausal women,
30-50 years of age,
BMI of 18.5 - 29.9 kg/m2,
Access to a smartphone that has a camera and iOS 11.0 or Android 4.2 and up,
Visible fine to moderate wrinkles on the face (e.g. forehead, crow's feet area, etc.),
Fitzpatrick scale of types I, II, & III
Urine pregnancy test of negative
Willing to maintain current physical activity and dietary habits
Willing to refrain from taking natural health products containing carotenoids (beta-carotene, lutein, lycopene, etc.)
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,
Willing to apply the moisturizer provided on every day throughout the study upon admission to the study (about -2 weeks),
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),
Able to understand and comply with requirements of the study (e.g. complete all clinical visits, questionnaires, records, and diaries),
Able to provide a written informed consent.

Exclusion Criteria:

Known immunodeficiency (immuno-compromised and immuno-suppressed participant; e.g. AIDS, lymphoma, participants undergoing long-term corticosteroid treatment, chemotherapy and allograft participant),
Known chronic or acute illness (e.g. hepatitis, diabetes, high blood pressure, jaundice, etc.), unless under control via medication,
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),
Known chronic or acute skin condition on the face (e.g. eczema, psoriasis, severe acne, rosacea, etc.),
Facial surgery (e.g. lifting, facial rejuvenation) or chemical treatment (e.g. Botox injection) within 5 years before study start,
Frequent tanning salons, use tanning products, or foresee high exposure to the sun during the study,
Tattoos on the face or palms of the hands,
Milk, soy or yeast allergy,
Routine use of dietary supplements that may interfere with outcomes measured (e.g. anti-oxidant, anti-inflammatory, herbal),
Use of probiotic products in the past 2 weeks (may be eligible to participate after a 2-week washout period),
Allergy to any of the ingredients contained in the moisturizer provided,
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),
Current smoker (tobacco or cannabis),
Excessive alcohol consumption (>1 drink/day),
Drug abuse or addiction,
Bleeding/blood disorder
Psychological disorder
Currently enrolled in another trial
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),
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