The goal of this clinical trial is to learn whether a natural marine supplement called NT-II™ (Salmon Undenatured Type II Collagen) can help lower knee discomfort caused by physical activity in otherwise healthy adults. Many active people experience knee pain when performing daily movements like climbing stairs, walking long distances, or squatting, even if they do not have a medical diagnosis such as arthritis. This discomfort can limit mobility, impact exercise routines, and reduce overall quality of life. This study is being conducted to determine whether NT-II™, taken as a once-daily oral supplement, can reduce this type of activity-related knee discomfort more effectively than a commonly used joint supplement containing glucosamine and chondroitin.
The main questions the study aims to answer are:
Does NT-II™ reduce knee discomfort caused by repeated activity over a 12-week period?
Does NT-II™ improve movement and quality of life compared to glucosamine-chondroitin?
Researchers will compare two different doses of NT-II™ (240 mg and 480 mg) to glucosamine (1500 mg) plus chondroitin (1300 mg), which is used as an active comparator. All three products will be taken once daily for 12 weeks.
Participants will:
Take their assigned supplement daily by mouth for 12 weeks
Track knee discomfort once per week using a pain rating scale called a visual analog scale (VAS) while doing an activity that usually causes discomfort, such as climbing stairs, walking, or squatting
Complete short surveys online about joint function, pain, and quality of life (including KOOS and SF-12 questionnaires)
Use a mobile app to perform simple knee range of motion tests at home
Wear a fitness tracker to monitor daily physical activity, such as step count and stair climbing
Collect two small blood samples at home using a finger-prick kit to check for changes in inflammation-related biomarkers
This study is for U.S.-based adults between the ages of 20 and 65 who are in generally good health but have had mild to moderate knee discomfort caused by physical activity for at least three months. The pain must be triggered by specific weight-bearing movements and be relieved by rest. Participants must not have osteoarthritis, rheumatoid arthritis, or other joint diseases. Individuals with recent knee injuries, major surgeries, or injections in the past six months cannot take part. Participants should not be using NSAIDs, turmeric, collagen, or other joint-related supplements during the study.
All study activities will take place remotely using a secure digital platform. There are no in-person clinic visits required. Eligible participants will receive all study materials by mail, including supplements, a wearable device, and an at-home blood sample collection kit. They will also be given access to a secure digital platform (Alethios) where they can complete questionnaires, enter pain ratings, and receive study instructions. Study staff will monitor progress, check for missing data, and assist participants through secure communication tools built into the platform.
The primary outcome of the study is the change in participant-reported knee discomfort, measured using a nominated activity VAS score (VASNA), from baseline to week 12. Additional outcomes will explore changes in function, mobility, physical activity, heart rate variability, and inflammatory biomarkers. The Pain Catastrophizing Scale (PCS) will also be used to examine whether thoughts and feelings about pain influence symptom reporting and treatment response.
This trial is sponsored by Hofseth BioCare ASA and is being conducted entirely online to improve access, lower participant burden, and support real-world understanding of joint health supplements. Study results may inform the use of NT-II™ as a marine-based nutritional strategy to support joint comfort in active individuals.
Adults aged 20 to 65 years.
Self-reported, reproducible knee discomfort associated with any knee-loading activities for at least 3 months prior to screening.
Discomfort must occur in at least one knee during a nominated aggravating activity at least twice per week and subside with rest.
VAS rating of 30 mm to 75 mm during the past week for the nominated activity.
Persistent knee pain at rest or recent acute lower-limb trauma.
Diagnosed structural or inflammatory joint disorders.
Current or recent physiotherapy targeting knee pain (within 6 months).
Allergy to fish or any study product ingredients.
Parallel
NT-II™ (240 mg)
Dietary supplementA once-daily capsule containing 240 mg of NT-II™, a marine-derived undenatured type II collagen supplement obtained from enzymatically processed salmon cartilage and bone. Taken orally for 12 weeks.
NT-II™ 480 mg
Dietary supplementTwo capsules of NT-II™ (each 240 mg), taken orally once daily for a total of 480 mg/day over 12 weeks. Sourced from salmon bone and cartilage to support joint health via oral tolerance.
Glucosamine/Chondroitin
Dietary supplementA combined dietary supplement containing 1500 mg glucosamine and 1300 mg chondroitin, taken orally once daily for 12 weeks. This supplement serves as the active comparator and is widely used to support joint structure and function.
Change in participant-nominated activity-related knee discomfort (VASNA for pain) from baseline to week 12
Each participant will identify a specific weight-bearing activity (e.g., stair descent, walking, or squatting) that consistently causes knee discomfort. Pain intensity will be rated on a 100 mm visual analog scale (VAS) for that activity at baseline and again at week 12. The primary outcome is the change in VASNA score from baseline to week 12.
Longitudinal Change in Nominated VAS
Participants will rate knee discomfort weekly using a 100 mm visual analog scale (VAS) for their nominated aggravating activity. Mixed-effects models will assess changes over time and treatment group-by-time interactions, including linear and nonlinear patterns.
Cumulative symptom improvement assessed by Incremental Area Under the Curve (iAUC) of weekly Nominated VAS
The incremental area under the curve (iAUC) will be calculated for weekly Nominated VAS scores from baseline to Week 12 to evaluate cumulative symptom improvement across all treatment arms.
KOOS Subscale Changes
Change from baseline to Week 6 and Week 12 in subscale scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS), including Pain (9 items), Symptoms (7 items), Activities of Daily Living (17 items), Sport and Recreation Function (5 items), and Knee-related Quality of Life (4 items). Each item is rated using a 5-point Likert scale, from 0 ("No problems") to 4 ("Extreme problems"). Subscale scores are calculated as the sum of item scores, then transformed to a 0-100 scale, where 0 represents extreme knee problems and 100 represents no problems. Subscales are analyzed separately to evaluate domain-specific effects across treatment arms.
KOOS Item-Level Functional Response
Change from baseline to Week 6 and Week 12 in selected item-level responses from the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Items reflect functional aspects of pain, symptoms, and mobility, including: Pain (Items 1, 4, 9), Symptoms (Items 2, 3, 7), Activities of Daily Living (Items 1, 4, 9, 10), Sport and Recreation Function (Items 3, 4), and Quality of Life (Items 1-4). Each item is rated using a 5-point Likert scale from 0 ("No problems") to 4 ("Extreme problems"), with scores transformed to a 0-100 scale where higher scores indicate better outcomes. Between-group differences in activity-specific pain and function patterns will be explored to assess targeted effects of treatment.
Smartwatch-Derived Sleep Quality Score (Exploratory)
Sleep quality will be assessed using composite scores derived from smartwatch data, including metrics such as total sleep time, sleep efficiency, and time in different sleep stages (e.g., deep, light, REM). A standardized sleep quality index will be calculated and compared between participants receiving NT-II™ (any dose) and those receiving glucosamine-chondroitin. Unit of Measure: Composite sleep quality score (0-100; higher scores indicate better sleep quality)
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