CLINICAL TRIAL PROTOCOL (NIH-STYLE)
Title
Randomized Controlled Trial of NAD⁺ Augmentation on Metabolic and Functional Outcomes in Adults With Prediabetes
Overall Objective
To determine whether NAD⁺ augmentation improves metabolic function, mitochondrial performance, and clinical outcomes in humans.
Specific Aims
Aim 1
Determine whether NAD⁺ augmentation improves insulin sensitivity in adults with prediabetes.
Hypothesis
NAD⁺ augmentation will significantly improve insulin sensitivity compared to placebo.
Aim 2
Evaluate the effect of NAD⁺ augmentation on mitochondrial and metabolic function.
Hypothesis
NAD⁺ augmentation will improve markers of mitochondrial function and metabolic efficiency.
Aim 3
Assess functional and physiologic outcomes.
Hypothesis
NAD⁺ augmentation will improve physical performance, energy utilization, and cardiometabolic parameters.
Study Design
Prospective Randomized Double-blind Placebo-controlled Parallel-group
Population
Inclusion Criteria
Age 40–70 Prediabetes (HbA1c 5.7–6.4) BMI 25–40
Exclusion Criteria
Insulin-dependent diabetes Severe organ failure (CHF NYHA IV, ESRD, active malignancy) Contraindications to infusion therapy
Sample Size
n = 120 participants
60 NAD⁺ group 60 placebo group
Power calculated to detect clinically meaningful change in insulin sensitivity
Intervention
Experimental Group
Intravenous NAD⁺ infusion Standardized dosing protocol (e.g., weekly infusions for 12 weeks, then maintenance)
Control Group
Placebo infusion (normal saline)
Duration
Primary endpoint: 6 months Extended follow-up: 12 months
Primary Outcome
Change in insulin sensitivity (HOMA-IR or hyperinsulinemic clamp)
Secondary Outcomes
HbA1c Fasting glucose Lipid profile Body composition VO2 max Resting energy expenditure Inflammatory markers NAD⁺ levels
Exploratory Outcomes
Continuous glucose monitoring Heart rate variability Physical activity data AI-based physiologic pattern analysis
Data Collection
Baseline
Full metabolic panel Functional testing Body composition NAD⁺ levels
Follow-up
Monthly labs 3-month and 6-month functional testing Continuous wearable monitoring
Statistical Analysis
Intention-to-treat Between-group comparisons Repeated measures ANOVA / mixed models Adjustment for confounders
Innovation
First controlled trial evaluating IV NAD⁺ in humans Direct translation of NAD⁺ biology into clinical intervention Integration of physiologic and metabolic endpoints
Significance
This study directly tests whether restoring NAD⁺ levels can modify metabolic dysfunction in humans, addressing a central mechanism implicated in aging and chronic disease.
Future Directions
If successful, this study will support:
Larger multicenter trials Extension into cardiovascular, neurologic, and aging populations Development of NAD⁺-targeted therapies