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

Sponsor

Prof Gérard WAEBER (Other)

Overall Status

Terminated

CT.gov ID

NCT03191201

Collaborator

Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland (Other), Centre Hospitalier Universitaire Vaudois (Other), University of Lausanne (Other)

Enrollment

Location

Arms

32.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Iron-deficiency Iron Toxicity Glucose Metabolism Disorders (Including Diabetes Mellitus) Metabolic Side Effects of Drugs Metabolic Disorder, Glucose Safety Issues	Drug: Ferric Carboxymaltose Drug: 0.9% sodium chloride solution	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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:

Double (Participant, Outcomes 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.

Primary Purpose:

Other

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.

Actual Study Start Date :

Jun 21, 2017

Actual Primary Completion Date :

Mar 9, 2020

Actual Study Completion Date :

Mar 9, 2020

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Change from baseline in glucose homeostasis status, assessed by a dynamic two-step hyperglycaemic clamp investigation. [at 28 days of the injection of the Investigation Product]
two-step hyperglycaemic clamp investigation

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Policlinique Médicale Universitaire	Lausanne	Vaud	Switzerland	1011

Sponsors and Collaborators

Prof Gérard WAEBER
Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
Centre Hospitalier Universitaire Vaudois
University of Lausanne

Investigators

Study Director: Gérard Waeber, MD, Centre Hospitalier Universitaire Vaudois (CHUV)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Prof Gérard WAEBER, Head of the Department of Medicine, University of Lausanne

ClinicalTrials.gov Identifier:

NCT03191201

Other Study ID Numbers:

2016-01449

First Posted:

Jun 19, 2017

Last Update Posted:

Mar 26, 2020

Last Verified:

Mar 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Prof Gérard WAEBER, Head of the Department of Medicine, University of Lausanne

Metabolomics, Transcriptomics, Ironomics

Additional relevant MeSH terms:

Metabolic Diseases

Glucose Metabolism Disorders

Disease

Metabolic Side Effects of Drugs and Substances

Study Results

No Results Posted as of Mar 26, 2020