Efficacy of Topical Niacinamide Riboside on the Signs of Facial Skin Aging

ChromaDex, Inc.140 enrolled

Overview

Niacinamide riboside (topical NR, also known as nicotinamide riboside) is an endogenous compound and a precursor (building block) to the essential cellular co-enzyme, nicotinamide adenine dinucleotide (NAD+). Research published by Maussudi et al. 2012 demonstrated that skin NAD+ levels were negatively correlated with age in both males and females, and aged skin was also correlated to an increase in DNA damage. Therefore, it is proposed that supporting skin NAD+ with precursors such as NR may be a strategy to combat DNA damage that leads to undesirable signs of skin aging, thus supporting skin cell resilience. The use of NR as a dietary supplement has produced effective, efficient, and reproducible increases in NAD+ in humans. However, the role of topically applied NR for skin aging requires further investigation. Though not measuring NAD+ directly, this study will explore if topically applied NR reduces the signs of skin aging that may result from cellular NAD+ deficiency. It is hypothesized that the addition of NR to a general skin care regimen will result in healthier, more youthful appearing skin over 12 weeks. The goal of this interventional clinical trial is to identify the most effective, tolerable, and efficient dose of NR for attenuating quantitative and qualitative indicators of facial skin aging in women ages 30-60. The three primary outcome measures are * Changes in skin biological age, * Quantitative reduction in fine lines and wrinkles near the eye, and * Changes in skin firmness and tightening. Secondary quantitative and qualitative outcomes include * Changes to pores, texture, redness, skin tone evenness, radiance, plumpness, and firmness on the global face. * Changes in skin moisture and skin barrier integrity, and * Participant perception of perceived efficacy, acceptability, and irritation. Skin imaging will also be employed in the study. Participants will be randomized into one of four test product groups: * Placebo * 2.5% NR, * 5% NR, or * 10% NR. The test product will be provided in a dry nanofiber sachet, and the percentage of NR is an estimate based on the final concentration of the applied material when mixed in serum. Following facial cleansing with the provided cleanser, study participants will prepare the test product (immediately before application) by dissolving a single sachet in the provided standardized gel serum. Following application, participants will apply the provided moisturizer and UV serum. Product application will occur twice daily for 84 days (12 weeks). In-clinic assessments will be performed at baseline and days 28, 56, and 84. Participants will also complete at home questionnaires on days 14 and 42. Adverse events and responses will be documented in participant diaries and immediately reported to the clinical research team.

Eligibility

Sex: FEMALEMin age: 30 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Open to all races provided they meet the inclusion and exclusion criteria below: * Gender: Female * Age: 30 to 60 years old * Phototype: I to VI * Subject presenting with fines lines/ wrinkles as Crow's feet, inclusion grade ≥ 3 and ≤ 6 on a 10-points scale. * Subject presenting with one or more visible signs of skin aging on face (example of signs of skin aging: wrinkles and fine lines, lack of firmness, lack of radiance, pigmented spots, dry and rough skin, visible pores, skin sagging). * Subject is not currently using NAD+ or another product containing Vitamin B3 (niacin, niacinamide, nicotinamide, nicotinamide riboside, nicotinamide mononucleotide, myristyl nicotinate, etc.) administered topically, orally intravenously, or through any form of injection, as a part of their current routine or 4 weeks before starting study. The only permitted exception is the use of a multivitamin that contains niacin or nicotinamide. If this is the case, the product and dose of niacin or nicotinamide should be documented at screening and continuation of use of the product should be documented at each site visit. * Willingness to maintain current lifestyle, wellness and skin care routines (with the exception of the inclusion of the product requirements incorporated into the study protocol). Exclusion Criteria: * Subject not providing consent; * Subject not complying with protocol requirements; * Subject of whom a health condition has changed since the inclusion visit in the I.E.C database, making the subject ineligible or places her at undue risk; * Active cancer diagnosis or diagnosis of cancer of any kind less than three years since remission, liver disease, kidney disease, or uncontrolled diabetes; * Pregnancy, actively breastfeeding, or not willing to take necessary precautions to avoid a pregnancy during the study; * Subject having a medical treatment, recent vaccination or expecting to be vaccinated during the study, that makes the subject ineligible or places her at undue risk, in particular, medical treatment (either oral or topical) containing tretinoin or isotretinoin during the 3 months before the starting day of the study; * Subject having a background of intolerance or allergy to cosmetics, NAD+ or any vitamin B3 derivative, ingredients in the auxiliary products or to other substances that makes the subject ineligible or places her at undue risk; * Subject having visible traces of irritation or any other abnormality on the concerned area; * Subject having skin recently exposed to excessive sunlight (natural or artificial) within 4 weeks preceding the inclusion; * Subject having undergone surgery, chemical or physical treatment to the concerned area in the last 12 months (no injection during the last 6 months); * Subject having applied anti-wrinkle/anti-aging/firming products on concerned area during the 4 weeks before the starting day of the study; * Subject having had any cosmetic procedures performed in the last six months (including Botox, peels, laser, etc.); * Subject having applied NAD+/B-vitamin products on the concerned area during the 4 weeks before the starting day of the study; * Subject having modified his/her cosmetic habits (on the concerned area by the study) during the last 2 weeks, making her ineligible; * Subject having applied cosmetic or pharmaceutical products (other than their usual cleanser) to the areas of concern during the 96 hours before the starting day of the study and on the day of inclusion; * Subject having applied any cosmetic or pharmaceutical products (only water allowed) to the areas of concern the day of inclusion.

Outcomes

Primary Outcomes

Change in skin's biological age

Dermal curette sampling of the skin at baseline and day 84 to evaluate changes in epigenetic markers of skin aging.

Time frame: baseline and day 84

Quantitative change in fine lines and wrinkles

The severity of fine lines and wrinkles will be clinically scored by a trained assessor evaluating 1) the Crow's feet area near the eye, and 2) the area underneath the eye, separately. Scoring for each area will range from 0 to 9, and intermediate scores (including fractions and decimals) will not be allowed. A score of 0 will indicate "no wrinkles," whereas a score of 9 will indicate "very marked wrinkles, accounting for number, surface and depth."

Time frame: baseline and days 28, 56, and 84

Quantitative changes in skin firmness and tightness

Changes in skin firmness and tightness will be measured by a Cutometer™ to objectively assess and compare the effect of the product on the skin's biomechanical properties. The device measures the deformation of a cutaneous area, submitted to a mechanical suction and its recovering power (Wilhelm et al., 1993). The skin viscoelastic properties are directly correlated to skin suppleness, elasticity, tonicity and firmness. The measurement will take place in the hollow of the cheek, providing a tactile measurement.

Time frame: baseline and days 56 and 84

Secondary Outcomes

Skin hydration

Skin hydration as measured by the Corneometer™ and the ewameter™. Measurements of the skin electrical capacitance by a Corneometer assesses the epidermal upper layers water content and quantifies the moisturizing effect of topical products. Measurement of TransEpidermal Water Loss (T.E.W.L. by aTewameter) is a non-invasive method to assess the integrity of the stratum corneum barrier function, by quantifying the water exchanges between the skin and the environment. Damage of the stratum corneum results in an increase in the T.E.W.L., leading to a more pervious skin.

Time frame: baseline and day 28

Moisture retention

Moisture retention is measured by a Tewameter™. Measurement of TransEpidermal Water Loss (T.E.W.L. by Tewameter™) is a non-invasive method to assess the integrity of the stratum corneum barrier function, by quantifying the water exchanges between the skin and the environment. Damage of the stratum corneum results in an increase in the T.E.W.L., leading to a more pervious skin. This method enables to assess and compare the protective effect of cosmetic investigational product(s) on the cutaneous barrier, after repeated applications, in the adult subject.

Time frame: baseline and day 28

Skin barrier integrity

Skin barrier integrity is measured by Tewameter™. Measurement of TransEpidermal Water Loss (T.E.W.L. by Tewameter™) is a non-invasive method to assess the integrity of the stratum corneum barrier function, by quantifying the water exchanges between the skin and the environment. Damage of the stratum corneum results in an increase in the T.E.W.L., leading to a more pervious skin. This method enables to assess and compare the protective effect of cosmetic investigational product(s) on the cutaneous barrier, after repeated applications, in the adult subject.

Time frame: baseline and day 28

Pores

A clinical evaluation of pore severity will be scored by a trained assessor. Grading will involve the use of a visual digital photographic scale designed by Qima-Newtone and the Institut d'Expertise Clinique (IEC) will assess pores on the cheek, in the area close to the nose wing. A standardized six point grading scale will be used (0-5), with a grade of 5 indicating greater severity.

Time frame: baseline and days 28, 56, and 84

Texture/smoothness

Skin texture homogeneity of the whole face will be scored by trained assessor. The participant will sit in front of the assessor under controlled conditions. A score range of 0-9, based on visual observations, will be determined. A score of 0 indicates "very heterogeneous skin (rough aspect and/or dilated pores), not uniform skin grain," whereas a score of 9 indicates "very homogeneous skin, same skin grain aspect on the concerned area."

Time frame: baseline and days 28, 56, and 84

Skin tone evenness

Clinical evaluation of visible color disorders/color imperfection will be evaluated by a trained assessor with the subject sitting in front of the assessor under controlled conditions. A score of 0 to 9 will be determined (no intermediate scores, such as fractions or decimals) will be allowed. A score of 0 indicates "no color imperfections (diffuse rednesses and/or brown shades and/or pigmented spots...)," whereas a score of 9 indicates "very marked color imperfections (diffuse rednesses and/or brown shades and/or pigmented spots...), very visible."

Time frame: baseline and days 28, 56, and 84

Skin plumpness

Clinical evaluation of skin plumpness will be evaluated by a trained assessor with the subject sitting in front of the assessor under controlled conditions. A score of 0 to 9 will be determined (no intermediate scores, such as fractions or decimals) will be allowed. A score of 0 indicates "not plump skin, lack of matter, fleshless, emaciated," whereas a score of 9 indicates "very plump skin, chubby."

Time frame: baseline and days 28, 56, and 84

Radiance

Clinical evaluation of whole face skin radiance will be evaluated by a trained assessor with the subject sitting in front of the assessor under controlled conditions. A score of 0 to 9 will be determined (no intermediate scores, such as fractions or decimals) will be allowed. A score of 0 indicates "not radiant skin, dull, does not reflect the light, not homogeneous, coarse skin grain and/or unhealthy glow," whereas a score of 9 indicates "very radiant skin, luminous, reflects the light, homogeneous, fine skin grain and/or healthy glow."

Time frame: baseline and days 28, 56, and 84

Redness

Clinical evaluation of redness visibility will be evaluated by a trained assessor with the subject sitting in front of the assessor under controlled conditions. A score of 0 to 9 will be determined (no intermediate scores, such as fractions or decimals) will be allowed. A score of 0 indicates "no redness visible," whereas a score of 9 indicates "lots of redness visible."

Time frame: baseline and days 28, 56, and 84

Firmness

Clinical evaluation of skin firmness in the hollow are of the cheek will be evaluated by a trained assessor with the subject sitting in front of the assessor under controlled conditions. A score of 0 to 9 will be determined (no intermediate scores, such as fractions or decimals) will be allowed. A score of 0 indicates "not firm skin, "flabby,"" whereas a score of 9 indicates "very firm skin, "hard.""

Time frame: baseline and days 28, 56, and 84

Participant Reported Outcome: Efficacy and acceptability of product

Self-assessment questionnaires regarding perceived efficacy and acceptability of product using a Likert response scale. The questionnaires will be provided during clinic visits and at-home assessments.

Time frame: baseline and days 14, 28, 42, 56, and 84

Adverse Event Monitoring

Adverse events will be monitored at all clinical visits. Participants will be asked immediately report any adverse reaction or any unresolved reactions or skin changes that occur during and after the study is over. Participants will document the adverse reaction, including their interpretation of the severity and time to resolution in their diaries. All suspected adverse events experienced by the participants are to be reported to the Investigator within 48 hours of occurrence, regardless of severity and resolution. The Investigator or designee will evaluate all product-related AEs as to their severity and causality, using standardized definitions.

Time frame: Up to two weeks after study completion

Efficacy of Topical Niacinamide Riboside on the Signs of Facial Skin Aging

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts