Cobalt BiokineticsNCT01990794

90-Day Cobalt Supplementation Study to Investigate the Cobalt Body Burden in Ten Healthy Adult Volunteers

An observational study of Cobalt Biokinetics and Safety of Cobalt Dietary Supplementation, run by Cardno ChemRisk.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to investigate steady-state cobalt levels following dietary supplementation for 90 days with 1 mg cobalt/day (as cobalt chloride in solution) in healthy adult volunteers. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Cobalt Biokinetics, Safety of Cobalt Dietary Supplementation
How many people: 13 participants
Where: No sites listed yet
Study dates: Jun 2012to Jul 2013
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Study population: Healthy adult volunteers from work site and off work site

Who may be able to join

Subject ≥ 18 years old.
Subject able to understand and willing to sign a written informed consent form for the study.

Who cannot join

Subject is unwilling to discontinue current multivitamins or other types of dietary supplements while on study
Subject has a documented history of an allergy to cobalt
Subject has a documented history of severe cardiac problems (e.g., congestive heart failure, myocardial ischemia within past 12 months, cardiomyopathy)
Subject has a documented history of thyroid, kidney, or liver disease
Subject has insulin-dependent diabetes
Subject has a concurrent illness or personal stressor which in the opinion of the investigator may interfere with the subject's ability to perform the study's requirements.

Show all 10Show fewer

Subject has a total joint replacement (e.g., knee, hip, shoulder)
Subject is pregnant or breastfeeding
Subject is unwilling to follow protocol requirements
Subject weight is less than 45 kg

About this study

Official title: A 90-Day Cobalt Supplementation Study to Investigate the Cobalt Body Burden in Ten Healthy Adult Volunteers

The purpose of this study is to investigate steady-state cobalt levels following dietary supplementation for 90 days with 1 mg cobalt/day (as cobalt chloride in solution) in healthy adult volunteers.

Read the detailed description

Over the counter cobalt (Co) dietary supplements are available for sale in the United States, but little is known regarding their clinical effects and biokinetic distribution and body burden with long-term use. This study assessed blood kinetics, steady-state levels, biochemical responses, and clinical effects in five adult males and five adult females who voluntarily ingested approximately 1.0 mg Co/day of a commercially available Co supplement over a three month period. Volunteers were instructed to take the Co-dietary supplement in the morning according to the manufacturer's label. Blood samples were collected and analyzed for a number of biochemical parameters before, during, and after dosing. Hearing, vision, cardiac, and neurological functions were also assessed in volunteers before, during, and after dosing.

Conditions: Cobalt Biokinetics, Safety of Cobalt Dietary Supplementation
Keywords: Cobalt, Dietary Supplements, Hematological, Thyroid
Medical subject headings: Thyroid Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01990794
Study group	Role	What they receive
Study Volunteers		Volunteers (males and females) were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label, which suggested a serving of 1 mg cobalt (~2 mL) daily "in water or juice as maintenance." Dietary supplementation lasted for approximately three months.

What is being measured

The primary outcome is the main question the study is designed to answer.

Cobalt Whole Blood Concentrations
The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing.
Measured: Before, during and after cobalt supplementation
Cobalt Serum Concentrations
The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing.
Measured: Before, during and after cobalt supplementation

Secondary outcomes (35)

Albumin Bound Cobalt Fraction in Serum
The fraction of albumin bound cobalt in serum was determined one to two weeks pre-dosing and on the day of the first dose before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, Day 88/90 and the fraction of albumin bound cobalt in serum was also determined at one and two weeks post-dosing.
Measured: Study volunteers will be followed for the duration of the study, an average of about 8 months for most volunteers
Effects on the Immune System
Sensitivity to metals before and after cobalt supplementation was assessed by an in vitro lymphocyte transformation test (LTT) performed at week 0 and after three months of cobalt supplementation. The average proliferation rate for each metal treatment was normalized to individual proliferation rates of untreated control cells which generated a stimulation index (SI). According to the manufacture, the SI ranges from 0-15, with an SI from 2 to 4 indicated mild reactivity, from 5 to 8 indicated moderate reactivity, and >8 indicated high reactivity to the metal. The data is presented as the averaged normalized lymphocyte transformation response to each metal in men and women combined (n = 10).
Measured: 0 weeks and three months
Hemoglobin Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Changes in Audiological Function
Audiologic assessments including pure tone threshold determination at frequencies ranging from 250 to 16000 Hz were performed with volunteers serving as their own baseline controls for receptive changes during the study (i.e., week 0, ~day 45, ~day 90). Audiologic assessments including a pure-tone threshold determination at frequencies that ranged from 250 to 16000 Hz were performed with volunteers serving as their own baseline controls for receptive changes during the study. Decreases in hearing were considered clinically significant when one of the following 3 American Speech-Language-Hearing Association criteria were met: 1) a ≥20-dB decrease in the pure-tone threshold at one test frequency, 2) a ≥10-dB decrease at 2 adjacent test frequencies, or 3) the loss of 3 consecutive test frequencies where responses were previously obtained.
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Cardiac Function
Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function
Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Neurological Function (Peroneal Motor Amplitude)
Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks).
Measured: Baseline, at the study midpoint, and at the study completion
White Blood Cell (WBC) Levels After 1, 2 and 3 Months of Cobalt Dietary Supplementation
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Red Blood Cell (RBC) Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Hematocrit Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Protein Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Albumin Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Thyroid-Stimulating Hormone (TSH) Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
T4 Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Total Iron Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Ferritin Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Creatine Creatine Kinase-Myocardial Band (CK-MB) Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Creatinine Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Alanine Aminotransferase (ALT) Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Aspartate Aminotransferase (AST) Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
HDL Cholesterol Levels After 3 Months of Cobalt Supplementation
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. HDL cholesterol levels were assessed before cobalt dietary supplementation and after three months of supplementation.
Measured: Study volunteers were assessed before and at the end of cobalt supplementation
Total Cholesterol Levels After 3 Months of Cobalt Supplementation
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Total cholesterol levels were assessed before cobalt dietary supplementation and after three months of supplementation.
Measured: Study volunteers were assessed before and at the end of cobalt supplementation
Triglyceride Levels After 3 Months of Cobalt Supplementation
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Triglyceride levels were assessed before cobalt dietary supplementation and after three months of supplementation.
Measured: Study volunteers were assessed before and at the end of cobalt supplementation
Glucose Levels After 1, 2 and 3 Months of Dosing
Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose.
Measured: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Cobalt Urine Concentrations
A 24 hr urine collection for cobalt analysis was performed at Day 14/16, Day 43/44 and Day 88/90.
Measured: During cobalt supplementation
Cobalt Urine Concentrations After Cessation of Cobalt Supplementation
A 24 hr urine collection for cobalt analysis was performed on three volunteers (two females and one male) at one, two, six and ten weeks post-dosing. The one male volunteer provided three consecutive 24-hr urine samples at the one and two week post-dosing time points; data for individual urine collections were averaged together to give an average one and two week post-dosing data concentration.
Measured: After cobalt supplementation
Changes in Cardiac Function (LVEF)
Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Cardiac Function (LA Volume Index)
Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Average RNFL Thickness)
Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Average C:D Ratio)
Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Cup Volume)
Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (VFI)
Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Mean Deviation and PSD)
Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Neurological Function (Sural Sensory Amplitude)
Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks).
Measured: Baseline, at the study midpoint, and at the study completion
Changes in Neurological Function (Velocity)
Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks).
Measured: Baseline, at the study midpoint, and at the study completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Jul 2013

First posted21 Nov 2013 (estimated)
Study startJun 2012
Primary completionMar 2013
Study completionJul 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cobalt BiokineticsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01990794
Sponsor's protocol ID: CR103
Status last verified: Oct 2014
First submitted: 12 Nov 2013
Last updated: 6 Oct 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Tvermoes BE, Unice KM, Paustenbach DJ, Finley BL, Otani JM, Galbraith DA. Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d. Am J Clin Nutr. 2014 Mar;99(3):632-46. doi: 10.3945/ajcn.113.071449. Epub 2014 Feb 5.
PubMed 24500148

Study at a glance

From the registry record, last updated by the sponsor on 6 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 90-Day Cobalt Supplementation Study to Investigate the Cobalt Body Burden in Ten Healthy Adult Volunteers
ClinicalTrials.gov ID: NCT01990794
Acronym / sponsor ID: CR103
Conditions: Cobalt Biokinetics, Safety of Cobalt Dietary Supplementation
Keywords: Cobalt, Dietary Supplements, Hematological, Thyroid
Study type: Observational
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Cardno ChemRiskUniversity, hospital or other
Collaborators: DePuy Orthopaedics
Study start: Jun 2012
Primary completion: Mar 2013 (actual)
Study completion: Jul 2013 (actual)
First posted: 21 Nov 2013 (estimated)
Results: Posted 6 Oct 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to investigate steady-state cobalt levels following dietary supplementation for 90 days with 1 mg cobalt/day (as cobalt chloride in solution) in healthy adult volunteers.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Study Volunteers	–	–Volunteers (males and females) were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label, which suggested a serving of 1 mg cobalt (~2 mL) daily "in water or juice as maintenance." Dietary supplementation lasted for approximately three months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult
Study population: Healthy adult volunteers from work site and off work site

Key inclusion criteria (2 listed)

Subject ≥ 18 years old.
Subject able to understand and willing to sign a written informed consent form for the study.

Key exclusion criteria (10 listed)

Subject is unwilling to discontinue current multivitamins or other types of dietary supplements while on study
Subject has a documented history of an allergy to cobalt
Subject has a documented history of severe cardiac problems (e.g., congestive heart failure, myocardial ischemia within past 12 months, cardiomyopathy)
Subject has a documented history of thyroid, kidney, or liver disease
Subject has insulin-dependent diabetes

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Cobalt Whole Blood Concentrations
Time frame: Before, during and after cobalt supplementation
The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing.
Cobalt Serum Concentrations
Time frame: Before, during and after cobalt supplementation
The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing.

35 secondary outcomes

Albumin Bound Cobalt Fraction in Serum
Time frame: Study volunteers will be followed for the duration of the study, an average of about 8 months for most volunteers
Effects on the Immune System
Time frame: 0 weeks and three months
Hemoglobin Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Changes in Audiological Function
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Cardiac Function
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Neurological Function (Peroneal Motor Amplitude)
Time frame: Baseline, at the study midpoint, and at the study completion
White Blood Cell (WBC) Levels After 1, 2 and 3 Months of Cobalt Dietary Supplementation
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Red Blood Cell (RBC) Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Hematocrit Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Protein Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Albumin Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Thyroid-Stimulating Hormone (TSH) Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
T4 Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Total Iron Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Ferritin Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Creatine Creatine Kinase-Myocardial Band (CK-MB) Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Creatinine Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Alanine Aminotransferase (ALT) Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Aspartate Aminotransferase (AST) Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
HDL Cholesterol Levels After 3 Months of Cobalt Supplementation
Time frame: Study volunteers were assessed before and at the end of cobalt supplementation
Total Cholesterol Levels After 3 Months of Cobalt Supplementation
Time frame: Study volunteers were assessed before and at the end of cobalt supplementation
Triglyceride Levels After 3 Months of Cobalt Supplementation
Time frame: Study volunteers were assessed before and at the end of cobalt supplementation
Glucose Levels After 1, 2 and 3 Months of Dosing
Time frame: Study volunteers were assessed before, during and after cobalt supplementation (2 wk post)
Cobalt Urine Concentrations
Time frame: During cobalt supplementation
Cobalt Urine Concentrations After Cessation of Cobalt Supplementation
Time frame: After cobalt supplementation
Changes in Cardiac Function (LVEF)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Cardiac Function (LA Volume Index)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Average RNFL Thickness)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Average C:D Ratio)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Cup Volume)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (VFI)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Visual Function (Mean Deviation and PSD)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Neurological Function (Sural Sensory Amplitude)
Time frame: Baseline, at the study midpoint, and at the study completion
Changes in Neurological Function (Velocity)
Time frame: Baseline, at the study midpoint, and at the study completion

Results and safety

Results posted to the registry on 6 Oct 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Study Volunteers	13	10

Primary outcome: Cobalt Whole Blood Concentrations

Time frame: Before, during and after cobalt supplementation. Mean (Standard Deviation). Unit: µg Co/L

Measure	Female n = 5	Male n = 5
Day 4/5	14.6 (8.2)	7.4 (3.6)
Day 8/9	33.9 (24.0)	8.5 (6.9)
Day 14/16	29.9 (22.0)	13.8 (6.4)
Day 22/23	25.6 (17.8)	18.7 (11.3)
Day 29/30	37.1 (24.8)	19.3 (7.9)
Day 43/44	35.9 (27.1)	18.5 (10.5)
Day 57/58	40.7 (28.1)	20.3 (11.1)
Day 71/72	37.1 (33.7)	22.1 (11.5)

Population analysed: Participants that completed three months of cobalt supplementation

Primary outcome: Cobalt Serum Concentrations

Time frame: Before, during and after cobalt supplementation. Mean (Standard Deviation). Unit: µg Co/L

Measure	Female Cobalt Serum Concentrations n = 5	Male Cobalt Serum Concentrations n = 5
Day 4/5	23.3 (12.4)	11.0 (5.7)
Day 8/9	42.3 (33.4)	11.8 (9.7)
Day 14/16	42.5 (30.9)	20.4 (11.5)
Day 22/24	36.8 (24.2)	34.7 (23.1)
Day 29/30	53.9 (35.8)	23.9 (8.7)
Day 43/44	48.2 (34.5)	24.3 (16.5)
Day 57/58	34.9 (20.3)	24.1 (15.7)
Day 71/72	46.1 (40.8)	28.2 (18.0)

Population analysed: Participants that completed three months of cobalt supplementation

35 secondary outcomes are reported in the full results.

Adverse events

Time frame: During the study: 7-8 months (approximate length of the study). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Study Volunteers	0 of 13 (0%)	4 of 13 (30.8%)	Not reported

Limitations and caveats (from the sponsor): The primary limitation of our study was its small sample size. We believe the study was sufficiently robust because we evaluated effects on hematologic and thyroid variables, both of which have been identified as sensitive markers of cobalt exposure.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24500148Tvermoes BE, Unice KM, Paustenbach DJ, Finley BL, Otani JM, Galbraith DA. Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d. Am J Clin Nutr. 2014 Mar;99(3):632-46. doi: 10.3945/ajcn.113.071449. Epub 2014 Feb 5.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Galbraith, MD principal investigator

Cardno ChemRisk

David Galbraith, MD study director

Cardno ChemRisk

Questions about this trial

What is this clinical trial studying?

An observational study of Cobalt Biokinetics and Safety of Cobalt Dietary Supplementation, run by Cardno ChemRisk.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cobalt Whole Blood Concentrations (time frame: Before, during and after cobalt supplementation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01990794, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2014.