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

Prof Gérard WAEBER

Status and phase: Terminated; Phase 4

Conditions: Iron-deficiency; Iron Toxicity; Metabolic Disorder, Glucose; Glucose Metabolism Disorders (Including Diabetes Mellitus); Safety Issues; Metabolic Side Effects of Drugs

Treatments: Drug: Ferric Carboxymaltose; Drug: 0.9% sodium chloride solution

Study type: Interventional

Funder types: Other

Identifiers

NCT03191201

2016-01449

Details and patient eligibility

About

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.

Enrollment: 32 patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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).

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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32 participants in 2 patient groups, including a placebo group

Ferric carboxymaltose arm

Active Comparator group

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.

Treatment:

Drug: Ferric Carboxymaltose

Placebo arm

Placebo Comparator group

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.

Treatment:

Drug: 0.9% sodium chloride solution