Human Biomarkers for Assessing Copper Deficiency

This study is currently recruiting participants.
Verified July 2010 by Emory University
Sponsor:
Information provided by:
Emory University
ClinicalTrials.gov Identifier:
NCT01177579
First received: August 5, 2010
Last updated: June 21, 2011
Last verified: July 2010
  Purpose

Copper is an essential nutrient for humans and is cofactor in enzymes that participate in critical body functions. Insufficient copper can lead to hematological and neurological abnormalities that may be irreversible if left untreated. Copper deficiency is believed to be rare in the U.S. population because typical dietary intake is usually sufficient to meet requirements. More recent evidence suggests that specific populations may be susceptible to copper deficiency in cases where copper absorption in the gut is impaired following gastric surgery or in individuals with high intakes of zinc. Preliminary studies by us and others have identified significant levels of moderate and severe symptomatic copper deficiency in patients who have undergone weight loss (bariatric) gastric bypass surgery. Copper deficiency in humans is difficult to recognize and treat because current diagnostic tools rely on measures of plasma concentrations of copper and ceruloplasmin, which are neither sensitive nor specific for copper deficiency, and early warning blood markers (biomarkers) have not been identified. Recent developments indicate that copper chaperone molecules and cuproenzymes such as cytochrome C oxidase and superoxide dismutase may be more sensitive to changes in copper status, but there has been very little work done in humans. The studies outlined here are aimed at assessing copper status using these biomarkers in gastric bypass surgery patients who are at risk for symptomatic copper deficiency. In addition, patients identified to be deficient will be supplemented with copper and this treatment will be evaluated using biomarker concentrations. The findings of these studies should provide insight into the effectiveness of novel biomarkers to identify those at risk and to guide appropriate treatment to prevent serious and permanent morbidity due to copper deficiency.


Condition Intervention Phase
Copper Deficiency
Dietary Supplement: Copper gluconate
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
Official Title: Human Biomarkers for Assessing Copper Deficiency and Repletion: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • copper co-enzymes [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    expression of CCS, SOD and COX4 in blood samples


Secondary Outcome Measures:
  • blood copper concentrations [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 70
Study Start Date: November 2010
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Aim 1; Biomarkers
Blood concentrations of copper coenzymes will be monitored for 1 year
Experimental: Copper supplement Arm
4 mg or 8 mg copper will be compared in a randomized controlled study
Dietary Supplement: Copper gluconate
4 or 8 mg copper gluconate/day will be assessed for efficacy of copper repletion
No Intervention: Normal Controls
Normal subjects will be used to generate reference measures.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria for Bariatric Surgery Patients: 1) Subject has signed an informed consent; 2) The patient is at least 18 but not more than 65 years of age; 3) subject has a plasma copper level which is in the lowest third and fourth quartiles but not below 80ug/dL for women or below 70 ug/day in men; 4) The patient has a body mass index (BMI) between 18.5 and 55 kg/m2; 4) Patient had RYGB at Emory Bariatric Center between 1999 - 2009; and 6) subject is able to travel to Emory outpatient clinics for blood draw within 3 months of being contacted.

Exclusion criteria for Bariatric Surgery Patients: 1) subject has a plasma copper level which is lower than 80 ug/dL in women or less than 70 ug/dL in men, and/or exhibits significant hematologic or neurologic signs or symptoms (e.g. neutropenia, leukopenia, anemia, paresthesias, gait disturbances, severe weakness, vitamin B12, or thiamine deficiency) requiring further medical evaluation for micronutrient depletion; 2) Patient is pregnant; 3) patient has history of surgical revision or conversion of bariatric procedure; 4) patient has a history of hospitalization for acute illness in the previous 3 months; 5) patient has current active malignant neoplasm; or history of malignancy other than localized basal cell cancer of skin during previous 5 years.

Inclusion and Exclusion Criteria for Normal Controls: Subjects (n = 10) will have normal blood levels of copper. Criteria will be similar to that for the bariatric surgery cohort except that subjects should be normal weight [BMI between 20 - 30 kg/m2, to avoid the effects of obesity on copper status(15)] and should not have abdominal surgery or history of gastrointestinal disease.

Inclusion and Exclusion Criteria for Aim 2 Patients:

Subjects in Aim 2 will be identified from the Emory Bariatric Clinic population or from those subjects in Aim 1 whose plasma copper concentrations are in the deficient range (< 80 ug/dL for women and 70 ug/dL for men). Subjects will be notified about the study and their eligibility will be determined.

Inclusion criteria: 1) Subject has signed an informed consent for Aim 2; 2) subject has a plasma copper level determined in Aim 1 which is below 80 ug/dL for women and below 70 ug/dL for men; 3) subject is at least 18 but not more than 65 years of age; 4) Patient had RYGB at Emory Bariatric Center between 1999 - 2009; and 5) subject is able to travel to Emory outpatient clinics for blood draw within 3 months of being contacted.

Exclusion criteria: 1) subject exhibits significant neurologic signs or symptoms (e.g. paresthesias, gait disturbances, severe weakness; 2) subject exhibits deficiencies in vitamins B12, vitamin B6 or B1; 3) subject is pregnant; 4) subject has history of surgical revision or conversion of bariatric procedure; 5) subject has a history of hospitalization for acute illness in the previous 3 months; 6) subject has current active malignant neoplasm; or history of malignancy other than localized basal cell cancer of skin during previous 5 years; 7) subject has type 1 or type 2 diabetes mellitus.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01177579

Contacts
Contact: Nana Gletsu Miller, PhD 404-712-2033 ngletsu@emory.edu

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Nana Gletsu Miller, PhD     404-712-2033     ngletsu@emory.edu    
Principal Investigator: Nana Gletsu Miller, PhD            
Sponsors and Collaborators
Emory University
  More Information

No publications provided

Responsible Party: Emory University
ClinicalTrials.gov Identifier: NCT01177579     History of Changes
Other Study ID Numbers: 00006969
Study First Received: August 5, 2010
Last Updated: June 21, 2011
Health Authority: US: Institutional Reveiw Board

Keywords provided by Emory University:
Bariatric surgery, copper deficiency, biomarkers

Additional relevant MeSH terms:
Copper
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013