This is a decentralized, randomized, three-arm clinical trial evaluating the effects of NT-II™, a marine-derived undenatured type II collagen, on activity-related knee discomfort (ArKD) in otherwise healthy adults. The trial is sponsored by Hofseth BioCare ASA and conducted entirely virtually in the United States using the Alethios digital clinical trial platform.
Undenatured type II collagen has been studied for its role in promoting joint health, primarily through immune-mediated mechanisms that support oral tolerance and reduce inflammation in joint tissues. While the majority of existing evidence is based on UC-II®, derived from chicken sternum, NT-II™ offers a novel alternative derived from Norwegian Atlantic salmon (Salmo salar), embedded in a natural hydroxyapatite matrix. This study seeks to evaluate NT-II™ as a non-pharmacological intervention for individuals experiencing reproducible, activity-induced knee pain but without clinical joint disease.
Eligible participants are healthy U.S. adults aged 20 to 65, with body mass index (BMI) between 20.0 and 32.5 kg/m², who report activity-related knee discomfort of moderate intensity (VAS score 30-75 mm) for at least 3 months. Discomfort must be reliably triggered by specific knee-loading movements (e.g., stairs, squatting, walking) and relieved with rest. Individuals with clinically diagnosed osteoarthritis or recent joint injury are excluded.
Following screening and a one-week run-in period (with symptom tracking only), participants are randomized in a 1:1:1 ratio to receive one of three interventions for 12 weeks:
NT-II™ standard dose - 240 mg/day
NT-II™ high dose - 480 mg/day
Glucosamine (1500 mg) + Chondroitin (1300 mg) - active comparator
The primary endpoint is the change in self-reported knee discomfort on a participant-nominated visual analog scale (VASNA) - an activity-specific VAS ranging from 0 to 100 mm - from baseline to week 12. Participants nominate their most aggravating activity (e.g., stair descent), and VAS pain scores are collected weekly throughout the trial.
Secondary outcomes include:
Subscale scores from the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire
Range of motion assessments (via the validated Curovate app)
Health-related quality of life (SF-12)
Daily activity metrics (e.g., step count, floors climbed) via wearable devices
Heart rate variability (HRV) recovery time as a biomarker of physiological resilience
Pain Catastrophizing Scale (PCS) to assess psychological contributors to pain reporting
The study is open-label, with centralized, blinded data analysis for biomarkers and PROMs. Outcome data are collected entirely remotely via the Alethios platform, wearable devices, mobile apps, and at-home blood collection kits.
This trial will assess both dose-response effects of NT-II™ and its comparative effectiveness versus glucosamine-chondroitin. It is designed to generate high-quality clinical evidence for NT-II™ in a functional knee discomfort population, while also exploring digital trial infrastructure, decentralized methodologies, and personalized symptom reporting frameworks. By integrating subjective and objective metrics, the study aims to enhance understanding of nutritional joint interventions in real-world settings.
