Human Biomarkers for Assessing Copper Deficiency
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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 |
- copper co-enzymes [ Time Frame: 1 year ] [ Designated as safety issue: No ]expression of CCS, SOD and COX4 in blood samples
- 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 |
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| Contact: Nana Gletsu Miller, PhD | 404-712-2033 | ngletsu@emory.edu |
| 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 | |
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