Ferric Carboxymaltose in Type 2 Diabetes Mellitus (T2DM) Patients With Iron Deficiency

Study Overview
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Brief Summary
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The purpose of this study is to investigate the correlation between HbA1c and iron status in Type 2 Diabetes mellitus patients with iron deficiency by intravenous substitution of iron.

Official Title
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Intravenous Ferric Carboxymaltose for Improvement of Metabolic Parameters and Vascular Function in T2DM-patients With Iron Deficiency

Conditions
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Type 2 Diabetes Mellitus, Iron Deficiency

Intervention / Treatment
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* Drug: ferric carboxymaltose
* Drug: NaCl (0,9%)


Participation Criteria
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Eligibility Criteria
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T2DM patients with diagnosis of ID defined as follows: serum ferritin <150 ng/mL or TSAT <25% if Hb < 14 g/dL serum ferritin <100 ng/mL or TSAT <20% if Hb ≥ 14 g/dL and ≤ 15g/dL] HbA1c: ≥ 6.5 to < 8.5 % Age > 18 years Written informed consent has been obtained. Exclusion Criteria: Continuous subcutaneous insulin infusion (CSII) thalassaemia Hb > 15 g/dL (> 9,31 mmol/L) Change of HbA1c of more than ±0,3 % within the last 3 months. known sensitivity to ferric carboxymaltose history of acquired iron overload History of erythropoietin stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 12 weeks prior to randomisation History of oral iron therapy at doses ≥ 100 mg/day 1 week prior to randomisation. Note: Ongoing oral use of multivitamins containing iron < 75 mg/day is permitted. Body weight ≤ 40 kg CRP > 15 mg/L Chronic liver disease (including known active hepatitis) and/or screening alanine transaminase (ALAT) or aspartate transaminase (ASAT) > 3 x ULN (upper limit of the normal range). Subjects with known hepatitis B surface antigen positivity and/or Hepatitis C virus ribonucleic acid positivity. Vitamin B12 and/or serum folate deficiency. If deficiency corrected subject may be rescreened for inclusion. Subjects with known seropositivity to human immunodeficiency virus. Clinical evidence of current malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia. Currently receiving systemic chemotherapy and/or radiotherapy. Renal dialysis (previous, current or planned within the next 6 months). Renal function GFR < 30 mL/min/ 1.73m2 (severe) Unstable angina pectoris as judged by the Investigator; severe valvular or left ventricular outflow obstruction disease needing intervention; atrial fibrillation/flutter with a mean ventricular response rate at rest >100 beats per minute. Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack or stroke within the last 3 months prior to randomisation. Coronary-artery bypass graft, percutaneous intervention (e.g., cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomisation. Patients with a polyneuropathy without ischemia. Subject of child-bearing potential who is pregnant (e.g., positive human chorionic gonadotropin test) or is breast feeding. Any subject not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication. Participation in other interventional trials Female subject of child-bearing potential who is pregnant (e.g., positive human chorionic gonadotropin test) or is breast feeding. Failure to use highly-effective contraceptive methods Persons with any kind of dependency on the investigator or employed by the sponsor or investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ferric carboxymaltose<br>Dose: according to SmPC; Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous | Drug: ferric carboxymaltose<br>* Dose:according to SmPC Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous<br>* Other names: Ferinject (marketing authorization number: 66227.00.00);|
| Placebo Comparator: NaCl (0,9%)<br>Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous | Drug: NaCl (0,9%)<br>* Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reduction in HBA1c-levels | reduction of HbA1c from week 1 (baseline) to week 13 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement of haematological and iron status | Hb, MCV, MCH, hypochromic cells, reticulocyte Hb content, ferritin, transferrin, transferrin saturation (TSAT), sTFR, iron, hepcidin | 12 weeks | 
| improvement in quality of life | potential clinical improvement and improvement in quality of life (EQ5D) of patients with ID T2DM | 12 weeks | 
| Improvement of metabolic status | measurement of fasting glucose, fructosamine | 12 weeks | 
| reliability of HbA1c-measurements | measurement of HbA1c in week 0; 5 and 13 | 12 weeks | 
| improvement in vascular function | Improvement in vascular function on the basis of the biomarker ADMA serum level | 12 weeks | 
| Change in used insulin dosage during study | Change in used insulin dosage during study (via patient diary) | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, iron deficiency