A Double Blind Randomised Placebo-controlled Trial to Assess the Role of Iron Repletion in Glucose Homeostasis. (DIAFER)

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.

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.

Study Overview

• Status: Terminated
• Conditions: Iron-deficiency; Safety Issues; Metabolic Disorder, Glucose; Iron Toxicity; Glucose Metabolism Disorders (Including Diabetes Mellitus); Metabolic Side Effects of Drugs
• Intervention / Treatment: Drug: Ferric Carboxymaltose; Drug: 0.9% sodium chloride solution

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Policlinique Medicale Universitaire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ferric carboxymaltose arm; 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.	Drug: Ferric Carboxymaltose; Ferric Carboxymaltose 1000 mg iron element will be diluted in 250 mL of a commercially available sterile 0.9% sodium chloride solution.
PLACEBO_COMPARATOR: Placebo arm; 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.	Drug: 0.9% sodium chloride solution; 250 mL of a commercially available sterile 0.9% sodium chloride solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in glucose homeostasis status, assessed by a dynamic two-step hyperglycaemic clamp investigation.	two-step hyperglycaemic clamp investigation	at 28 days of the injection of the Investigation Product

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 14 days	plasma hs-CRP levels	at 14 days of the injection of the Investigation Product
Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 28 days	plasma hs-CRP levels	at 28 days of the injection of the Investigation Product
Change from baseline in interleukin-6 (IL-6) levels at 14 days	plasam IL-6 levels	at 14 days of the injection of the Investigation Product
Change from baseline in interleukin-6 (IL-6) levels at 28 days	plasam IL-6 levels	at 28 days of the injection of the Investigation Product
Change from baseline in adiponectin levels at 14 days	adiponectin	at 14 days of the injection of the Investigation Product
Change from baseline in adiponectin levels at 28 days	adiponectin	at 28 days of the injection of the Investigation Product
Change from baseline in interleukin-1beta levels at 14 days	IL-1b	at 14 days of the injection of the Investigation Product
Change from baseline in interleukin-1beta levels at 28 days	IL-1b	at 28 days of the injection of the Investigation Product
Change from baseline in blood pressure levels at 14 days	systolic and diastolic blood pressure	at 14 days of the injection of the Investigation Product
Change from baseline in blood pressure levels at 28 days	systolic and diastolic blood pressure	at 28 days of the injection of the Investigation Product
Change from baseline in the plasma lipid profile level at 14 days	plasma total- and HDL-cholesterol and plasam triglycerides	at 14 days of the injection of the Investigation Product
Change from baseline in the plasma lipid profile level at 28 days	plasma total- and HDL-cholesterol and plasam triglycerides	at 28 days of the injection of the Investigation Product
Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 14 days	Calculated Homeostasis Model Assessment (HOMA-2) index	at 14 days of the injection of the Investigation Product
Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 28 days	Calculated Homeostasis Model Assessment (HOMA-2) index	at 28 days of the injection of the Investigation Product

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the plasma metabolomic profiling as assessed by metabolomics	Metabolomics	at 14 and 28 days of the injection of the Investigation Product
Change from baseline in circulating miRNAs	selected miRNA as measured by qPCR	at 14 and 28 days of the injection of the Investigation Product

Collaborators and Investigators

• Sponsor: Prof Gérard WAEBER
• Collaborators: Centre Hospitalier Universitaire Vaudois; University of Lausanne; Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
• Investigators: Study Director: Gérard Waeber, MD, Centre Hospitalier Universitaire Vaudois (Chuv)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 21, 2017
• Primary Completion (ACTUAL): March 9, 2020
• Study Completion (ACTUAL): March 9, 2020

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (ACTUAL): June 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Metabolomics, Transcriptomics, Ironomics
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Disease; Drug-Related Side Effects and Adverse Reactions; Metabolic Diseases; Glucose Metabolism Disorders; Metabolic Side Effects of Drugs and Substances
• Other Study ID Numbers: 2016-01449

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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