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

Safety Issues Clinical Trial

— 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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03191201
• Other study ID #: 2016-01449
• Status: Terminated
• Phase: Phase 4
• Start date: June 21, 2017
• Est. completion date: March 9, 2020

Study information

• Verified date: March 2020
• Source: University of Lausanne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Disease
• Drug-Related Side Effects and Adverse Reactions
• Glucose Metabolism Disorders
• Glucose Metabolism Disorders (Including Diabetes Mellitus)
• Iron Toxicity
• Iron-deficiency
• Metabolic Diseases
• Metabolic Disorder, Glucose
• Metabolic Side Effects of Drugs
• Metabolic Side Effects of Drugs and Substances
• Safety Issues

Intervention

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.
• 0.9% sodium chloride solution
250 mL of a commercially available sterile 0.9% sodium chloride solution.

Locations

Country	Name	City	State
Switzerland	Policlinique Médicale Universitaire	Lausanne	Vaud

Sponsors (4)

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

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Change from baseline in circulating miRNAs	selected miRNA as measured by qPCR	at 14 and 28 days of the injection of the Investigation Product
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in adiponectin levels at 14 days	adiponectin	at 14 days of the injection of the Investigation Product
Secondary	Change from baseline in adiponectin levels at 28 days	adiponectin	at 28 days of the injection of the Investigation Product
Secondary	Change from baseline in interleukin-1beta levels at 14 days	IL-1b	at 14 days of the injection of the Investigation Product
Secondary	Change from baseline in interleukin-1beta levels at 28 days	IL-1b	at 28 days of the injection of the Investigation Product
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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