Back to resultsA Double Blind Randomised Placebo-controlled Trial to Assess the Role of Iron Repletion in Glucose Homeostasis. (DIAFER)
Primary Purpose
Iron-deficiency, Iron Toxicity, Glucose Metabolism Disorders (Including Diabetes Mellitus)
Status
Terminated
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Ferric Carboxymaltose
0.9% sodium chloride solution
Sponsored by
About this trial
This is an interventional other trial for Iron-deficiency focused on measuring Metabolomics, Transcriptomics, Ironomics
Eligibility Criteria
Inclusion Criteria:
- Premenopausal women.
- Negative pregnancy test.
- Adequate contraception during the study period and for 1 month following study completion.
- Overt or relative iron deficiency at screening defined as follows:
Serum ferritin <50 ng/mL AND transferrin saturation <20%, OR Serum ferritin <30 ng/mL.
- Serum C-reactive protein: <5 mg/L if not on oral contraception, OR <20 mg/L if use of oral contraception
- Intolerance to oral iron formulations, or lack of efficacy of oral iron formulations.
- Minimum total score of 5 on the Visual analogic scale of fatigue.
- Normal levels of vitamin B12 and folic acid at screening.
- Availability and willingness to complete all study visits and procedures per protocol.
- Ability to sign an informed consent.
Exclusion Criteria:
- Age <18 years.
- Menopause (defined as an amenorrhea of at least 12 months).
- Irregularly menstruating women (menstrual cycle outside a range of 24-38 days in duration) or experiencing overt metrorrhagia (simple spotting not being an exclusion criteria).
- Body mass index <18.5 kg/m2 or >30 kg/m2.
- Diabetes, defined as subjects with HbA1c ≥ 6.5 % and/or with fasting blood glucose levels ≥ 7 mmol/l and/or with a history of diabetes and/or by the use of anti-diabetic drugs.
- Hb level <117 g/L or known haemoglobinopathy or haemochromatosis.
- Blood transfusion within the last 12 weeks.
- Intake of iron preparations 4 weeks prior to screening.
- Known hypersensitivity to FCM or to any other iron preparation.
- Suspicion of major depressive disorder based on Patient Health Questionnaire.
- Known chronic inflammatory disease, including human immunodeficiency virus, hepatitis B or hepatitis C virus infection.
- Active malignancy.
- Decreased renal function (estimated glomerular filtration rate using the CKD-EPI equation<60 ml/min/1.73m2).
- Liver dysfunction (aspartate aminotransferase and alanine aminotransferase > 3-fold upper limit).
- Angina (Class IV).
- Asthma.
- Documented sleep apnoea.
- Important recent weight loss (>10% within the past month).
- Thyroid dysfunction (thyroid stimulating hormone >4 µU/mL).
- Reported weekly alcohol consumption > 14 standard drinks.
- Drug abuse (any drug consumption reported in the past 12 months).
Sites / Locations
- Policlinique Médicale Universitaire
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Ferric carboxymaltose arm
Placebo arm
Arm Description
Ferric carboxymaltose (FCM), 1000 mg iron element will be administered once by drip infusion (Intravenous route). FCM will be diluted in 250 mL of a commercially available sterile 0.9% sodium chloride solution prior to administration. Infusion time will be 15 minutes.
A commercially available sterile, 250 mL, 0.9% sodium chloride solution will be administered by drip infusion (Intravenous route). Infusion time will be 15 minutes. At the end of the randomised part of the study, participants initially randomised to the placebo group will be included in a non-blinded open-label extension part and receive a FCM 1000 mg injection.
Outcomes
Primary Outcome Measures
Change from baseline in glucose homeostasis status, assessed by a dynamic two-step hyperglycaemic clamp investigation.
two-step hyperglycaemic clamp investigation
Secondary Outcome Measures
Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 14 days
plasma hs-CRP levels
Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 28 days
plasma hs-CRP levels
Change from baseline in interleukin-6 (IL-6) levels at 14 days
plasam IL-6 levels
Change from baseline in interleukin-6 (IL-6) levels at 28 days
plasam IL-6 levels
Change from baseline in adiponectin levels at 14 days
adiponectin
Change from baseline in adiponectin levels at 28 days
adiponectin
Change from baseline in interleukin-1beta levels at 14 days
IL-1b
Change from baseline in interleukin-1beta levels at 28 days
IL-1b
Change from baseline in blood pressure levels at 14 days
systolic and diastolic blood pressure
Change from baseline in blood pressure levels at 28 days
systolic and diastolic blood pressure
Change from baseline in the plasma lipid profile level at 14 days
plasma total- and HDL-cholesterol and plasam triglycerides
Change from baseline in the plasma lipid profile level at 28 days
plasma total- and HDL-cholesterol and plasam triglycerides
Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 14 days
Calculated Homeostasis Model Assessment (HOMA-2) index
Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 28 days
Calculated Homeostasis Model Assessment (HOMA-2) index
Full Information
NCT ID
NCT03191201
First Posted
May 17, 2017
Last Updated
March 24, 2020
Sponsor
Prof Gérard WAEBER
Collaborators
Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland, Centre Hospitalier Universitaire Vaudois, University of Lausanne
1. Study Identification
Unique Protocol Identification Number
NCT03191201
Brief Title
A Double Blind Randomised Placebo-controlled Trial to Assess the Role of Iron Repletion in Glucose Homeostasis.
Acronym
DIAFER
Official Title
A Double Blind Randomised Placebo-controlled Trial to Assess the Effect of a Single Administration of Ferric Carboxymaltose of 1000 mg Iron on Glucose Homeostasis, in Iron-deficient Non-anaemic Women of Childbearing Age.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
The reason for early termination is difficulties recruiting that caused a premature ending of financial resources ensuring protected time for research.
Study Start Date
June 21, 2017 (Actual)
Primary Completion Date
March 9, 2020 (Actual)
Study Completion Date
March 9, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof Gérard WAEBER
Collaborators
Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland, Centre Hospitalier Universitaire Vaudois, University of Lausanne
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this study the investigators aim at addressing potential relationships between iron stores and glucose homeostasis. Iron (i.e. Ferric Carboxymaltose) will be perfused to pre-menopausal, iron-deficient non-anaemic women suffering from a chronic fatigue syndrome and parameters related to glucose homeostasis, parameters related to metabolic syndrome and inflammation will be measured before and after the intervention.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron-deficiency, Iron Toxicity, Glucose Metabolism Disorders (Including Diabetes Mellitus), Metabolic Side Effects of Drugs, Metabolic Disorder, Glucose, Safety Issues
Keywords
Metabolomics, Transcriptomics, Ironomics
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Double blind randomised placebo-controlled, parallel group comparative inferiority study with open-label extension divided in two parts:
A first randomised and double-blind part in which FCM or placebo will be administered at baseline and post-baseline parameters assessed.
A second non-randomised, non-blinded open-label extension part starting at the end of part 1, in which participants randomised to the placebo group will receive a FCM injection and post-baseline parameters assessed.
Masking
ParticipantOutcomes Assessor
Masking Description
To ensure that patients are unaware of the study drug they are receiving, the infusion pouch will be prepared in a separate room by members of the pharmacy unit and opaque bags will cover the infusion kits and infusions will be done via dark coloured infusion sets. Finally, a curtain will be used to shield the injection site from the patient's view.
To ensure that Outcomes Assessors are unaware of the study drug the patient is receiving, a seperate team of care providers will supervise the infusion of the investigation product and collect and/or manage adverse events (AEs) and serious adverse events (SAEs). The Outcome Assessor will not have access to participant related data during the randomised part of the study.
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ferric carboxymaltose arm
Arm Type
Active Comparator
Arm Description
Ferric carboxymaltose (FCM), 1000 mg iron element will be administered once by drip infusion (Intravenous route). FCM will be diluted in 250 mL of a commercially available sterile 0.9% sodium chloride solution prior to administration. Infusion time will be 15 minutes.
Arm Title
Placebo arm
Arm Type
Placebo Comparator
Arm Description
A commercially available sterile, 250 mL, 0.9% sodium chloride solution will be administered by drip infusion (Intravenous route). Infusion time will be 15 minutes.
At the end of the randomised part of the study, participants initially randomised to the placebo group will be included in a non-blinded open-label extension part and receive a FCM 1000 mg injection.
Intervention Type
Drug
Intervention Name(s)
Ferric Carboxymaltose
Intervention Description
Ferric Carboxymaltose 1000 mg iron element will be diluted in 250 mL of a commercially available sterile 0.9% sodium chloride solution.
Intervention Type
Drug
Intervention Name(s)
0.9% sodium chloride solution
Intervention Description
250 mL of a commercially available sterile 0.9% sodium chloride solution.
Primary Outcome Measure Information:
Title
Change from baseline in glucose homeostasis status, assessed by a dynamic two-step hyperglycaemic clamp investigation.
Description
two-step hyperglycaemic clamp investigation
Time Frame
at 28 days of the injection of the Investigation Product
Secondary Outcome Measure Information:
Title
Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 14 days
Description
plasma hs-CRP levels
Time Frame
at 14 days of the injection of the Investigation Product
Title
Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 28 days
Description
plasma hs-CRP levels
Time Frame
at 28 days of the injection of the Investigation Product
Title
Change from baseline in interleukin-6 (IL-6) levels at 14 days
Description
plasam IL-6 levels
Time Frame
at 14 days of the injection of the Investigation Product
Title
Change from baseline in interleukin-6 (IL-6) levels at 28 days
Description
plasam IL-6 levels
Time Frame
at 28 days of the injection of the Investigation Product
Title
Change from baseline in adiponectin levels at 14 days
Description
adiponectin
Time Frame
at 14 days of the injection of the Investigation Product
Title
Change from baseline in adiponectin levels at 28 days
Description
adiponectin
Time Frame
at 28 days of the injection of the Investigation Product
Title
Change from baseline in interleukin-1beta levels at 14 days
Description
IL-1b
Time Frame
at 14 days of the injection of the Investigation Product
Title
Change from baseline in interleukin-1beta levels at 28 days
Description
IL-1b
Time Frame
at 28 days of the injection of the Investigation Product
Title
Change from baseline in blood pressure levels at 14 days
Description
systolic and diastolic blood pressure
Time Frame
at 14 days of the injection of the Investigation Product
Title
Change from baseline in blood pressure levels at 28 days
Description
systolic and diastolic blood pressure
Time Frame
at 28 days of the injection of the Investigation Product
Title
Change from baseline in the plasma lipid profile level at 14 days
Description
plasma total- and HDL-cholesterol and plasam triglycerides
Time Frame
at 14 days of the injection of the Investigation Product
Title
Change from baseline in the plasma lipid profile level at 28 days
Description
plasma total- and HDL-cholesterol and plasam triglycerides
Time Frame
at 28 days of the injection of the Investigation Product
Title
Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 14 days
Description
Calculated Homeostasis Model Assessment (HOMA-2) index
Time Frame
at 14 days of the injection of the Investigation Product
Title
Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 28 days
Description
Calculated Homeostasis Model Assessment (HOMA-2) index
Time Frame
at 28 days of the injection of the Investigation Product
Other Pre-specified Outcome Measures:
Title
Change from baseline in the plasma metabolomic profiling as assessed by metabolomics
Description
Metabolomics
Time Frame
at 14 and 28 days of the injection of the Investigation Product
Title
Change from baseline in circulating miRNAs
Description
selected miRNA as measured by qPCR
Time Frame
at 14 and 28 days of the injection of the Investigation Product
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Premenopausal women.
Negative pregnancy test.
Adequate contraception during the study period and for 1 month following study completion.
Overt or relative iron deficiency at screening defined as follows:
Serum ferritin <50 ng/mL AND transferrin saturation <20%, OR Serum ferritin <30 ng/mL.
- Serum C-reactive protein: <5 mg/L if not on oral contraception, OR <20 mg/L if use of oral contraception
Intolerance to oral iron formulations, or lack of efficacy of oral iron formulations.
Minimum total score of 5 on the Visual analogic scale of fatigue.
Normal levels of vitamin B12 and folic acid at screening.
Availability and willingness to complete all study visits and procedures per protocol.
Ability to sign an informed consent.
Exclusion Criteria:
Age <18 years.
Menopause (defined as an amenorrhea of at least 12 months).
Irregularly menstruating women (menstrual cycle outside a range of 24-38 days in duration) or experiencing overt metrorrhagia (simple spotting not being an exclusion criteria).
Body mass index <18.5 kg/m2 or >30 kg/m2.
Diabetes, defined as subjects with HbA1c ≥ 6.5 % and/or with fasting blood glucose levels ≥ 7 mmol/l and/or with a history of diabetes and/or by the use of anti-diabetic drugs.
Hb level <117 g/L or known haemoglobinopathy or haemochromatosis.
Blood transfusion within the last 12 weeks.
Intake of iron preparations 4 weeks prior to screening.
Known hypersensitivity to FCM or to any other iron preparation.
Suspicion of major depressive disorder based on Patient Health Questionnaire.
Known chronic inflammatory disease, including human immunodeficiency virus, hepatitis B or hepatitis C virus infection.
Active malignancy.
Decreased renal function (estimated glomerular filtration rate using the CKD-EPI equation<60 ml/min/1.73m2).
Liver dysfunction (aspartate aminotransferase and alanine aminotransferase > 3-fold upper limit).
Angina (Class IV).
Asthma.
Documented sleep apnoea.
Important recent weight loss (>10% within the past month).
Thyroid dysfunction (thyroid stimulating hormone >4 µU/mL).
Reported weekly alcohol consumption > 14 standard drinks.
Drug abuse (any drug consumption reported in the past 12 months).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gérard Waeber, MD
Organizational Affiliation
Centre Hospitalier Universitaire Vaudois (CHUV)
Official's Role
Study Director
Facility Information:
Facility Name
Policlinique Médicale Universitaire
City
Lausanne
State/Province
Vaud
ZIP/Postal Code
1011
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35706490
Citation
Jaccard E, Seyssel K, Gouveia A, Vergely C, Baratali L, Gubelmann C, Froissart M, Favrat B, Marques-Vidal P, Tappy L, Waeber G. Effect of acute iron infusion on insulin secretion: A randomized, double-blind, placebo-controlled trial. EClinicalMedicine. 2022 May 6;48:101434. doi: 10.1016/j.eclinm.2022.101434. eCollection 2022 Jun.
Results Reference
derived
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A Double Blind Randomised Placebo-controlled Trial to Assess the Role of Iron Repletion in Glucose Homeostasis.
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