Strength training intervention with creatine/whey protein supplementation vs placebo on frailty in older adults with cirrhosis (STRIVE): A Randomized Controlled Trial

Imagine a body that has lost its reserve, its ability to bounce back when life throws a curveball. In the medical world, this state is called frailty. It is not simply about being old or weak; it is a specific loss of physical strength and energy that makes a person vulnerable to falls, illness, and a rapid decline in health. For people living with cirrhosis, a condition where the liver is severely scarred and struggling to function, this vulnerability is compounded. Their bodies are often in a constant state of breakdown, burning through muscle faster than they can rebuild it. While doctors have long known that exercise and better nutrition can help, many patients with advanced liver disease are too sick to leave their homes for a gym, and standard advice often fails to reach those with the most severe forms of the disease. The question remains: can a simple combination of movement and specific food supplements help these vulnerable patients regain their strength?

To answer this, a team of researchers at the University of California, San Francisco, and the University of Alberta has launched a carefully planned study called STRIVE. This is not a study looking for a miracle cure, but rather a rigorous test of a practical strategy. The researchers are focusing on older adults, aged sixty and above, who have cirrhosis and show signs of frailty. They are testing whether adding two common supplements—creatine and whey protein—to a structured exercise program can make a measurable difference. Creatine is a substance found naturally in muscle that helps provide quick energy for movement, while whey protein is a high-quality food source that helps the body repair and build muscle tissue. While athletes have used these for decades, and older adults in the general population have seen benefits, no one has yet tested if this specific combination works for people with damaged livers.

The study is designed as a randomized controlled trial, which is the gold standard for medical research. Two hundred participants will be enrolled, and they will be divided into two groups. One group will receive the creatine and whey protein supplements, while the other will receive a placebo, a powder that looks and tastes the same but contains no active ingredients. Neither the patients nor the doctors will know who is getting which powder until the study is finished. This double-blind approach ensures that the results are based on the actual effects of the treatment, not on expectations. Before the main study begins, all participants go through a two-week "ramp-up" period. During this time, they learn to use a digital health application on a tablet or phone. This app guides them through a semi-supervised program that includes three main pillars: exercise, nutrition, and life skills.

The exercise portion is tailored to be safe and manageable at home. Participants watch pre-recorded videos showing them how to perform resistance exercises using resistance bands, along with short bursts of aerobic activity and stretching. They are asked to do this for thirty minutes, three days a week. The app also provides educational videos and interactive quizzes about nutrition and habits, such as setting goals and managing sleep. To ensure everyone can keep up, the program includes weekly check-ins with a doctor or exercise specialist to monitor progress and adjust the routine if needed. A nutritionist checks in every two weeks to offer personalized dietary advice. This digital structure is crucial because it allows patients with severe liver disease, who might be too frail to travel to a clinic, to participate safely from their own homes.

The researchers are measuring their success with a specific tool called the Liver Frailty Index. This test involves simple physical tasks: squeezing a handgrip device, standing up from a chair without using hands, and maintaining balance. These movements are direct indicators of how well the body is functioning. The primary goal of the study is to see if the group taking the supplements improves their scores on this test by at least a small, but meaningful, amount compared to the group taking the placebo. Beyond the physical tests, the team is also tracking how the patients feel about their own health, how active they are in their daily lives, and what they are eating. They will also measure changes in body composition, looking specifically at muscle mass and fat, using a device that sends a safe, low-level electrical current through the body to estimate these values.

Safety is a top priority throughout the process. Because creatine and protein can affect the kidneys and liver, the researchers will regularly check blood work to ensure the supplements are not causing harm. If a patient experiences significant side effects, such as severe swelling or digestive issues, the study team has a clear plan to reduce the dose or stop the supplements entirely while keeping the patient in the exercise program. The study is set to run for twelve weeks, a period long enough to see if the body begins to adapt and strengthen.

The hope behind this work is that if the combination of supplements and digital exercise proves effective, it could become a new standard of care for a population that currently has very few options. For older adults with cirrhosis, who face a high risk of hospitalization and death, even a small improvement in physical strength could mean the difference between remaining independent and becoming bedbound. By testing this approach in a controlled setting, the researchers aim to provide clear evidence on whether adding creatine and whey protein to a home-based exercise routine can truly help rebuild the strength of those with the most fragile livers. The results will not just tell us if the supplements work, but whether a digital, home-based model can successfully deliver complex medical care to those who need it most.