Copper Supplementation in Cirrhosis

NCT07471542 | Recruiting

• 2 other identifiers: STUDY000236861R01DK142802-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cirrhosis; Chronic Liver Disease; Fibrosis; Infection

Keywords

copper; cirrhosis; malnutrition

Outcome Measures

Primary Outcomes (1)

• Plasma copper (Cu) concentration

  The primary endpoint is the mean change in plasma Cu concentration between baseline and each intervention period

  From randomization to 1. end 6-week; 2. end of 9-week; 3. end of 15 week. First 6 week is intervention period 1 (either copper or placebo); followed by a 3-week washout period; followed by another 6-week intervention period (either placebo or copper).

Secondary Outcomes (14)

• Biomarkers of functional Copper (Cu) status

  From randomization to 1) end 6-week; 2) end of 9-week; 3) end of 15 week. First 6 week is intervention period 1 (either copper or placebo), followed by a 3-week washout period, followed by another 6-week intervention period (either placebo or copper)

• Biomarkers of functional copper status

  Time Frame: From randomization to 1) end 6-week; 2) end of 9-week; 3) end of 15 week. First 6 week is intervention period 1 (either copper or placebo), followed by a 3-week washout period, followed by another 6-week intervention period (either placebo or

• Biomarker of functional copper status

  Time Frame: From randomization to 1) end 6-week; 2) end of 9-week; 3) end of 15 week. First 6 week is intervention period 1 (either copper or placebo), followed by a 3-week washout period, followed by another 6-week intervention period (either placebo or

• Biomarker of functional copper status

  From randomization to 1. end 6-week; 2. end of 9-week; 3. end of 15 week. First 6 week is intervention period 1 (either copper or placebo); followed by a 3-week washout period; followed by another 6-week intervention period (either placebo or copper)

• Biomarker of functional copper status

  From randomization to 1) end 6-week; 2) end of 9-week; 3) end of 15 week. First 6 week is intervention period 1 (either copper or placebo), followed by a 3-week washout period, followed by another 6-week intervention period (either placebo or copper)

Study Arms (2)

Copper supplementation 1st arm

EXPERIMENTAL

copper supplementation first, washout, then placebo

Dietary Supplement: Copper Gluconate

Placebo first arm

EXPERIMENTAL

Placebo first, washout, then copper supplementation

Dietary Supplement: Copper Gluconate

Interventions

Copper Gluconate DIETARY_SUPPLEMENT

Oral copper gluconate 4 mg daily

Copper supplementation 1st arm; Placebo first arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients age 18 or older with confirmed diagnosis of cirrhosis based on clinical history, exam, imaging, laboratory or histological criteria;
• 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);
• 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 myelopathy, coagulopathy with spontaneous bleeding.

You may not qualify if:

• Patients with Wilson disease, cholestatic liver diseases including primary biliary cholangitis and primary sclerosing cholangitis, all of which are associated with Cu overload;
• Patients with fulminant hepatic failure;
• Renal failure with a creatinine clearance \<25 ml/minute;
• Hepatic encephalopathy more than grade 2 (Hepatic Encephalopathy in Chronic Liver Disease, 2014);
• MELD score \>25 to minimize subject dropout due to been too ill;
• Serious non-liver related medical illnesses such as cardiopulmonary and renal diseases and non-liver malignancies;
• Active alcohol use;
• Pregnancy

Sponsors & Collaborators

• University of Washington: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Alaska Fairbanks: collaborator

Study Sites (1)

University of Washington Medical Center

Seattle, Washington, 98195, United States

RECRUITING

Related Publications (4)

• Uauy R, Olivares M, Gonzalez M. Essentiality of copper in humans. Am J Clin Nutr. 1998 May;67(5 Suppl):952S-959S. doi: 10.1093/ajcn/67.5.952S.

  PMID: 9587135 BACKGROUND

• Dhanda A, Atkinson S, Vergis N, Enki D, Fisher A, Clough R, Cramp M, Thursz M. Trace element deficiency is highly prevalent and associated with infection and mortality in patients with alcoholic hepatitis. Aliment Pharmacol Ther. 2020 Aug;52(3):537-544. doi: 10.1111/apt.15880. Epub 2020 Jun 23.

  PMID: 32573823 BACKGROUND

• Yu L, Liou IW, Biggins SW, Yeh M, Jalikis F, Chan LN, Burkhead J. Copper Deficiency in Liver Diseases: A Case Series and Pathophysiological Considerations. Hepatol Commun. 2019 Jun 26;3(8):1159-1165. doi: 10.1002/hep4.1393. eCollection 2019 Aug.

  PMID: 31388635 BACKGROUND

• Yu L, Yousuf S, Yousuf S, Yeh J, Biggins SW, Morishima C, Shyu I, O'Shea-Stone G, Eilers B, Waldum A, Copie V, Burkhead J. Copper deficiency is an independent risk factor for mortality in patients with advanced liver disease. Hepatol Commun. 2023 Feb 20;7(3):e0076. doi: 10.1097/HC9.0000000000000076. eCollection 2023 Mar 1.

  PMID: 36809345 BACKGROUND

MeSH Terms

Conditions

Fibrosis; Infections; Malnutrition

Interventions

Gluconates

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Lei Yu, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Sissons-Ross

CONTACT

206-616-0397; lsissons@uw.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor, Medicine

Model Details: Randomized double blinded crossover trial

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 13, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (1)