Pilot Study to Evaluate the Effect of Nicotinamide Riboside on Immune Activation in Psoriasis

Background: Psoriasis causes chronic inflammation in the body. Researchers want to see if a kind of vitamin B3 dietary supplement can help. This might lead to more treatment options. Objective: To test if the dietary supplement nicotinamide riboside can improve immune system function in the blood and skin of people with mild to moderate psoriasis. Eligibility: People ages 18-80 with mild to moderate active psoriasis not currently treated with biological therapy Design: Participations will be screened with: Medical and medication history Physical exam Measure of body mass index Skin exam Blood and urine tests Participants will have visit 1. They will have repeats of the screening tests. They will also have 2 skin biopsies. These will be from both lesions and unaffected areas. The areas will be injected with a numbing medicine. A round cutting device will remove small pieces of skin from each area. Participants will take the study supplement or a placebo starting at the first visit. Neither participants nor the study team will know which they receive. Participants will take capsules twice daily for a total of 4 weeks. Participants will then have visit 2. This will include the tests performed at visit 1. Participants may by contacted by phone or email between visits to see how they are doing. If participants develop any side effects in the 7 days after they stop taking the capsules, they may have another visit.

Study Description: Psoriasis is a Th17 linked inflammatory disease and we find that the vitamin B3 analogue nicotinamide riboside (NR) blunts Th1 and Th17 activation in ex-vivo na(SqrRoot) ve and differentiated T cells from control and psoriasis subjects. These findings supported the proposal of the following hypothesis. Supplementation with NR will blunt systemic immune activation in mild/moderate psoriasis. Objectives: Evaluate the effect of NR on Th17 biology Explore the effect of NR on neutrophils, specifically lowdensity granulocytes Evaluate whether NR modulates keratinocyte activation in skin lesions in psoriatic subjects Evaluate the effect of NR on HDL regulated reverse cholesterol transport and lipid composition Endpoints: The primary outcome will be the change in the TH17 cell cytokine IL-17 secretion in response to T-cell differentiation comparing the baseline versus NR or placebo. The comparisons will be performed using paired two-tailed Student t-tests. Significance will be tested at the 0.05 alpha level in this pilot study. Secondary outcomes are: Evaluate the effect of NR on the T cell transcriptome Explore the effect of NR on low-density granulocytes and neutrophils Evaluate whether NR modulates keratinocyte activation in skin lesions in psoriatic subjects Evaluate the effect of NR on HDL regulated reverse cholesterol transport and lipid composition by NMR spectroscopy Study Population: Up to 40 male and female subjects of all races between the ages of 18-80 years with mild-moderate psoriasis who live locally will be screened. Phase: N/A Description of Sites/Facilities: Enrollment and study visits will take place at the NIH Clinical Center or via telehealth visits. Enrolling Participants: Psoriatic Subjects Description of Study Intervention: Nicotinamide Riboside Chloride 500mg or placebo twice daily by mouth for 28 days. Study Duration: 3 years Participant Duration: 5-23 weeks

Chronic Inflammatory Skin Disease, Systemic Inflammation-Induced Atherosclerosis, TH17 Cell Cytokine IL-17 Secretion in Response to T-cell Differentiation, Effect of NR on Neutrophils, Effect of NR on HDL

Subjects will take two capsules of nicotinamide riboside by mouth (250mg NR) twice daily for a total of 4 weeks.

Subjects will take two capsules of nicotinamide riboside by mouth (placebo) twice daily for a total of 4 weeks

Subjects will take two capsules of nicotinamide riboside by mouth (250mg NR or placebo) twice daily for a total of 4 weeks.

The primary outcome will be the change in the TH17 cell cytokine IL-17 secretion in response to T-cell differentiation comparing the baseline versus NR or placebo.

INCLUSION CRITERIA: Individuals must meet all inclusion criteria listed below in order to be eligible to participate in the study. Males and females between the ages of 18 and 80 with mild to moderate active psoriasis. Female subjects of child-bearing ability willing to commit to reliable contraception while participating in the study. Ability to provide informed consent Willingness and ability to participate in required study procedures EXCLUSION CRITERIA: Severe psoriasis by PASI (Psoriasis Area and Severity Index) score > 12 Currently being treated with biologic immune modifying agents. Currently on treatment for allergies or other inflammatory diseases. Currently taking a multivitamin, Vitamin B or tryptophan supplementation and unwilling to stop within 2 weeks of baseline visit. Unwillingness/inability to provide informed consent ALT > x3 upper limit of normal, hepatic insufficiency or active liver disease Recent history of acute gout Chronic renal insufficiency with creatinine > 2.5mg/dl Pregnant (or attempting to become pregnant) women Current participation in another drug study History of intolerance to NR precursor compounds, including niacin or nicotinamide Study adherence concerns Individuals with diabetes type 1 and 2 who use insulin Women of child-bearing potential unwilling to use contraception or unwilling to practice abstinence Breastfeeding women unwilling to stop breastfeeding Immunization administered within 30 days of participation and no plans for immunization while participating in the study