Nutrition and Swelling

This study is looking at whether taking a nutritional supplement before and after knee replacement surgery affects normal recovery. The supplement is Xcelerated Recovery (XR), an over-the-counter supplement made with essential amino acids (EAAs), which are building blocks of protein that the body cannot make on its own.

Participants aged 65 and older with planned knee replacement surgery, and signs of nutritional risk or reduced muscle strength on short screening questionnaires, will be invited to join. Participants are assigned by chance to one of two groups. One group receives usual care plus the XR supplement, taken twice a day starting 7 days before surgery and continuing for 14 days after surgery. The other group receives usual care without the supplement. Everyone in the study wears a small temporary skin sensor (similar to a temporary tattoo) on the knee and uses a smartphone app to take scans that measure knee size. Participants also have in-person visits before surgery and 2 weeks and 1 month after surgery.

The main goal is to measure how knee and leg size (circumference) changes after surgery in each group. Researchers will also look at muscle strength, knee movement, walking and mobility tests, and reported pain. This study is not testing the supplement as a treatment for any disease or medical condition. The results may help researchers better understand how nutrition relates to normal recovery after knee replacement surgery.

Background: Total knee arthroplasty (TKA) is followed by a normal recovery period that includes shifts in tissue fluid, loss of muscle, and reduced mobility. Perioperative nutrition guidance recommends adequate protein intake (at least 1.2 g/kg/day) to support muscle protein balance. Studies of essential amino acid (EAA) supplementation around the time of TKA have reported better preservation of muscle mass and functional mobility. However, few studies have examined over-the-counter EAA-based supplements, or their relationship to postoperative limb circumference. Wearable technologies, such as the InkWell temporary skin sensor, may allow standardized, convenient at-home measurement of limb circumference.

Purpose: This study evaluates the effect of perioperative EAA-based supplementation on normal physiological recovery after TKA. Xcelerated Recovery (XR), a commercially available EAA-based dietary supplement, is the study product. The primary measure is limb circumference, a marker of postoperative tissue fluid balance. XR also contains other ingredients, including creatine monohydrate and vitamins, so findings will apply to this formulation as a whole and not to EAAs alone. The study is not intended to evaluate the supplement's ability to diagnose, cure, mitigate, treat, or prevent any disease, including postoperative complications.

Design: This is a single-site (UCSF), randomized, two-arm interventional study. After informed consent and confirmation of eligibility, participants are randomized 1:1 using the REDCap randomization module to usual care plus XR or to usual care alone. The target enrollment is 80 participants. XR is taken twice daily (19.2 g of EAAs per serving, 38.4 g per day) from 7 days before surgery through 14 days after surgery.

Procedures: At a baseline visit about 7 days before surgery, the study team collects medical history, body mass index, nutrition and muscle-health screening questionnaires, knee and leg circumference measurements, knee range of motion, the Timed Up and Go test, the 10-meter walk test, quadriceps strength by handheld dynamometer, and a pain questionnaire. Participants in the supplement group receive XR and written instructions. All participants complete InkWell onboarding about 7 days before surgery, in person or by video. The study team contacts participants weekly by phone during the first month after surgery. In-person visits at 2 weeks and 1 month after surgery repeat the standardized measurements, and participants who received XR complete a supplement adherence questionnaire and return unused product. Participants also complete a postoperative recovery survey.

InkWell sensor: Participants in both groups wear a temporary skin sensor on the knee and use the InkWell Health smartphone app to scan it. Scans are completed daily from 7 days before surgery through postoperative day 7, then every other day through postoperative day 14. InkWell measurements are exploratory and are compared with the standardized in-person circumference measurements. The measurements are not used to make clinical decisions.

Analysis and safety: The primary analysis compares the change in circumference between groups, with adjustment for baseline values and relevant covariates. Strength, range of motion, function, and pain are compared between groups as secondary measures. Adverse events, postoperative complications, length of stay, and readmissions are collected for safety monitoring and summarized descriptively by group.