Randomized, Open-label, Safety Study of Subcutaneous and Intramuscular Injections of Niagen® Plus

Randomized, Open-Label, Safety Pilot Study of Multiple Subcutaneous and Intramuscular Injections of Niagen® Plus

The goal of this study is to learn about the safety of Niagen®Plus, an injectable form of nicotinamide riboside (NR), and to see how it affects levels of NAD+ in the blood. Niagen®Plus will be given either by subcutaneous (under the skin) or intramuscular (into the muscle) injection at two dose levels (50 mg or 100 mg).

The main questions this study aims to answer are:

Is Niagen®Plus safe and well-tolerated when given by injection several times over 100 days?

How do NAD+ levels in blood change after repeated doses of Niagen®Plus?

What are participants' and clinicians' experiences with the injections?

Researchers will also look at changes in fatigue, sleep, quality of life, inflammation markers, mitochondrial efficiency, and perceived skin appearance.

Participants will:

Receive three injections in clinic on Days 1-3, followed by a Day 10 follow-up visit

Self-inject Niagen®Plus at home three times per week from Days 10-100

Return to the clinic on Days 40 and 100 for safety and laboratory testing

Complete short surveys about fatigue, sleep, and overall well-being throughout the study

The study will include 40 generally healthy adults and will last about 100 days per participant.

Study Overview

• Status: Recruiting
• Conditions: Fatigue; Healthy Volunteer
• Intervention / Treatment: Drug: Niagen®Plus

Detailed Description

This is a single-site, prospective, randomized, open-label, parallel 4-arm pilot trial designed to evaluate the safety and pharmacodynamic effects of Niagen®Plus (nicotinamide riboside chloride, NRCl) when administered by injection. The study includes two phases over approximately 100 days per participant.

In Phase 1, participants receive three consecutive daily injections of Niagen®Plus (50 mg or 100 mg; subcutaneous or intramuscular) administered in clinic on Days 1-3, followed by a Day 10 follow-up visit for safety evaluation and laboratory testing. In Phase 2, participants continue self-administration of subcutaneous Niagen®Plus at home three times per week (Monday, Wednesday, Friday) through Day 100, returning to the clinic on Days 40 and 100 for repeat safety assessments, sample collection, and exploratory analyses.

Primary endpoints assess safety and tolerability through vital signs, comprehensive metabolic and hematologic panels (CMP, CBC, homocysteine), and adverse-event monitoring. Secondary endpoints include changes in whole-blood NAD⁺ concentrations measured by dried-blood-spot analysis and clinician- and participant-reported injection experience. Exploratory endpoints include fatigue, energy, sleep, and quality-of-life assessments; plasma biomarkers of inflammation (C-reactive protein); phenotypic age calculation; oxidative stress testing (in urine); mitochondrial efficiency testing; and subjective evaluations of skin appearance.

The target enrollment is 40 generally healthy adults (10 per arm). The study is not powered for hypothesis testing but will inform the design of subsequent placebo-controlled trials by characterizing safety profiles, pharmacokinetic trends, and feasibility of at-home administration.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Anne Russ, M.S.; Phone Number: 13058482347; Email: research@impacthealthteam.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33180
      • Recruiting
      • BTT Medical Institute Aventura North
      • Contact: Robert Mogel; Phone Number: +1 (609) 915-9639; Email: rmogel@bttcorp.com
      • Contact: Karolline Catoira; Phone Number: 7867071444; Email: research@impacthealthteam.com
      • Principal Investigator: Halland Chen, M.D.
      • Sub-Investigator: James Clement, J.D., L.L.M., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Generally healthy adults, aged 18+
• Demonstrated baseline fatigue as determined by a below average score from the FAS (threshold prespecified in SAP).
• NAD+ or NAD+ precursor injection naïve (including intravenous, intramuscular, subcutaneous, or other injection route) (i.e., 8 weeks abstinent)
• Non-anemic
• Willingness to adhere to lifestyle considerations and study procedures.
• Ability to read English, and provide written informed consent.
• Willingness to self-administer the study material, via subcutaneous injection for 90 days (days 10-100 of the study), and complete finger prick blood collections.

Exclusion Criteria:

• One or more uncontrolled chronic illness including but not limited to diabetes, cardiovascular disease, liver, disease, kidney disease, or any form of cancer. An uncontrolled chronic illness, in this case, is defined as any changes to medication or other treatment modalities in the last 90 Days.
• More than one chronic disease diagnosis under active treatment.
• Any chronic disease, as determined by the primary investigator, that increases risk or confounds safety.
• Any acute illness within 14 Days prior to Visit 1 (Day 1).
• Cancer diagnosis within the last 5 years
• Anemia (as defined by hemoglobin levels below 100 g/L, and other blood measures)
• Current pregnancy or lactation; unwilling to use effective contraception if of childbearing potential.
• Use of any NAD+ supplement, NAD+ precursor, or vitamin B3 product, orally, nasally, by patch, or injection within the last 60 Days. NAD+ precursors and related compounds include niacin (NA), nicotinamide (NAM), nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), NAD+, NADH, NAD+3, inositol hexanicotinate, apigenin; etc. The exception is the use of a daily oral multivitamin, that may contain vitamin B3 (niacin/nicotinamide). Such use will need to be documented.
• Hypersensitivity or allergy to NR, niacin, other forms of vitamin B3/NAD+ precursors, bacteriostatic water
• Significant aversion to needles or finger pricks.
• Participation in another clinical intervention study, 90 Days (or 5 half-lives of the intervention, whichever is longer) prior to Visit 1 (Day 1).
• Any other condition rendering the participant unsuitable per investigator.
• Excessive daily use of alcohol, defined as 4 or more drinks on one occasion, or illicit drug use which would prevent adherence to the protocol as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 mg Subcutaneous Niagen®Plus; Participants receive 50 mg Niagen®Plus administered subcutaneously (under the skin) once daily for three consecutive days during in-clinic visits (Days 1-3). Participants then continue self-administered subcutaneous injections of the same dose three times per week (Monday, Wednesday, Friday) from Days 10-100.	Drug: Niagen®Plus; Pharmaceutical-grade nicotinamide riboside chloride (NRCl), compounded for sterility and reconstituted in bacteriostatic water for injection. Administered by subcutaneous or intramuscular injection at 50 mg or 100 mg per dose. Participants receive three clinician-administered injections during clinic visits on Days 1-3, followed by at-home subcutaneous self-administration three times per week (Monday, Wednesday, Friday) from Days 10-100, depending on study arm.
Experimental: 100 mg Subcutaneous Niagen®Plus; Participants receive 100 mg Niagen®Plus administered subcutaneously once daily for three consecutive days during in-clinic visits (Days 1-3). Participants then continue self-administered subcutaneous injections of the same dose three times per week (Monday, Wednesday, Friday) from Days 10-100.	Drug: Niagen®Plus; Pharmaceutical-grade nicotinamide riboside chloride (NRCl), compounded for sterility and reconstituted in bacteriostatic water for injection. Administered by subcutaneous or intramuscular injection at 50 mg or 100 mg per dose. Participants receive three clinician-administered injections during clinic visits on Days 1-3, followed by at-home subcutaneous self-administration three times per week (Monday, Wednesday, Friday) from Days 10-100, depending on study arm.
Experimental: 50 mg Intramuscular Niagen®Plus; Participants receive 50 mg Niagen®Plus administered intramuscularly (into the deltoid muscle) once daily for three consecutive days during in-clinic visits (Days 1-3). No further at-home injections are performed; participants return for follow-up visits on Days 10, 40, and 100.	Drug: Niagen®Plus; Pharmaceutical-grade nicotinamide riboside chloride (NRCl), compounded for sterility and reconstituted in bacteriostatic water for injection. Administered by subcutaneous or intramuscular injection at 50 mg or 100 mg per dose. Participants receive three clinician-administered injections during clinic visits on Days 1-3, followed by at-home subcutaneous self-administration three times per week (Monday, Wednesday, Friday) from Days 10-100, depending on study arm.
Experimental: 100 mg Intramuscular Niagen®Plus; Participants receive 100 mg Niagen®Plus administered intramuscularly (into the deltoid muscle) once daily for three consecutive days during in-clinic visits (Days 1-3). No further at-home injections are performed; participants return for follow-up visits on Days 10, 40, and 100.	Drug: Niagen®Plus; Pharmaceutical-grade nicotinamide riboside chloride (NRCl), compounded for sterility and reconstituted in bacteriostatic water for injection. Administered by subcutaneous or intramuscular injection at 50 mg or 100 mg per dose. Participants receive three clinician-administered injections during clinic visits on Days 1-3, followed by at-home subcutaneous self-administration three times per week (Monday, Wednesday, Friday) from Days 10-100, depending on study arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events	The incidence and severity of treatment-associated moderate and severe adverse events (AEs) will be assessed.	From Day 1 (first injection) through Day 100 (final visit)
Blood Pressure	Blood pressure, systolic and diastolic, will be measured	Immediately before the first intervention, and through the 100th day of the study.
Heart Rate	Heart rate will be measured.	Immediately before the intervention and through the 100th day of the study (final visit).
Pulse Rate	Pulse rate will be measured.	Immediately before and through the 100th day of the study (final visit).
Respiratory Rate	Respiratory rate will be measured.	Immediately before and through the 100th day of the study (final visit).
Blood Oxygen	Blood oxygen level will be measured.	Immediately before and through the 100th day of the study (final visit).
Complete Blood Count	A complete blood count with differential will be evaluated through whole blood samples	Immediately before and through the 100th day of the study (final visit).
Comprehensive Metabolic Panel	Comprehensive metabolic panel will be evaluated through whole blood samples	Immediately before and through the 100th day of the study (final visit).
Homocysteine	Homocysteine will be measured from venous blood samples as part of the primary safety laboratory panel. Levels will be analyzed as absolute values and change-from-baseline to evaluate any clinically significant elevations or shifts associated with repeat dosing of Niagen®Plus.	Immediately before and through the 100th day of the study (final visit).
High-Sensitivity C-Reactive Protein (hs-CRP)	High-sensitivity C-reactive protein will be assessed from venous blood samples as part of the primary safety laboratory panel. hs-CRP is a sensitive biomarker of systemic inflammation and may signal acute or sub-acute inflammatory responses to repeated Niagen®Plus dosing. Levels will be analyzed as absolute values and change-from-baseline to identify any clinically meaningful elevations or trends. Data will be summarized descriptively by dose and route of administration to support safety evaluation.	Immediately before and through the 100th day of the study (final visit).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in whole-blood NAD⁺ concentrations	Quantitative change in whole-blood NAD⁺ levels measured by dried blood spot (DBS) assay at baseline and follow-up visits to characterize pharmacodynamic response to Niagen®Plus administration.	Baseline (Day 1) through Day 100
Participant- and clinician-reported injection-site experience	Numeric rating scale (0-10) and clinician assessments of pain, erythema, swelling, and induration to characterize tolerability of subcutaneous versus intramuscular administration.	Immediately post-injection through 180 minutes after dosing (Days 1-3)

Collaborators and Investigators

• Sponsor: ChromaDex, Inc.

Publications and helpful links

General Publications

• Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019 Jul 5;9(1):9772. doi: 10.1038/s41598-019-46120-z.

Helpful Links

• Commercial listing of the same compounded product (Niagen Plus injection) that is being used as the investigational product.
• Laboratory assay measuring mitochondrial efficiency from dried blood spots, used as an exploratory endpoint in the study.
• The current study's previous clinical trial with unpublished results.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): February 15, 2026
• Study Completion (Estimated): February 15, 2026

Study Registration Dates

• First Submitted: November 3, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Fatigue
• Other Study ID Numbers: IH-NP-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. De-identified aggregate data and summary results will be shared with the sponsor and may be included in publications or presented at scientific meetings.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No