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

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.

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).