A Pilot Randomized Controlled Trial to Determine the Biochemical Effect, Safety and Patient Reported Outcomes of Copper Supplementation in Patients With Cirrhosis
University of Washington
Summary
End stage liver disease or cirrhosis is a major cause of mortality in the United States and the world. Other than targeting the underlying cause, such as alcohol cessation and antiviral therapy, very few medical treatments can change the natural history of cirrhosis. Malnutrition is one of the few potentially modifiable factors that have been associated with cirrhosis severity and poor prognosis. The transition metal copper (Cu) is an essential trace metal that must be acquired from diet. Its metabolism is primarily regulated by the liver in its role as a master regulator of nutrients. In 2019, the investigators reported that Cu deficiency defined by below normal serum or liver concentrations occurred in a wide range of liver disorders and was associated with a severe disease phenotype. Improvement in liver function was observed in 2 of the 3 patients who received Cu supplementation. In 2023, the investigators conducted a longitudinal cohort study utilizing clinical, serum and liver explant tissue data from 183 cirrhosis patients. The investigators showed that Cu deficiency was associated with 2-fold higher infection rate and a more than 3-fold increase in the risk of death compared to patients with normal Cu status. These preliminary findings and the well-established importance of Cu in human health prompted the investigators to design the current pilot randomized, placebo-controlled, crossover trial to determine the effect of Cu supplementation on Cu dependent biochemical changes, patient safety and patient reported outcomes in cirrhosis.
Description
Approximately 41,000 people die annually of chronic liver disease (CLD) including liver cancer in the United States. Compared to other chronic diseases, patients with CLD have high rates of healthcare utilization and death. The annual cost of care for patients with cirrhosis, the most advanced stage of liver disease, is approximately $21 billion. While liver transplantation is a curative, albeit costly, treatment, there are far fewer donors than patients in need of liver transplants. Other than targeting the causes of cirrhosis, such as alcohol cessation and antiviral therapy, very few medical…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Adult patients age 18 or older with confirmed diagnosis of cirrhosis based on clinical history, exam, imaging, laboratory or histological criteria; 2. Cirrhosis patients whose serum or plasma Cu are below the normal range (80-155 ug/dL for women and 70-140 ug/dL for men); 3. Cirrhosis patients whose serum or plasma Cu are in the normal range but exhibit at least one clinical feature that has been associated with Cu deficiency. These include history of infections, unexplained anemia, severe leukopenia, iron overload, unexplained neurological symptoms such as ataxia or my…
Interventions
- Dietary SupplementCopper Gluconate
Oral copper gluconate 4 mg daily
Location
- University of Washington Medical CenterSeattle, Washington