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

Phase 4

Terminated

• Conditions: Iron-deficiency; Metabolic Disorder, Glucose; Iron Toxicity; Glucose Metabolism Disorders (Including Diabetes Mellitus); Metabolic Side Effects of Drugs; Safety Issues
• Interventions: Drug: 0.9% sodium chloride solution; Drug: Ferric Carboxymaltose

• Registration Number: NCT03191201
• Lead Sponsor: Prof Gérard WAEBER

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-17
• Study First Submitted QC: 2017-06-15
• Study First Posted: 2017-06-19
• Study Start: 2017-06-21
• Status Verified: 2020-03
• Primary Completion: 2020-03-09
• Study Completion: 2020-03-09
• Last Update Submitted: 2020-03-24
• Last Update Posted: 2020-03-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 32

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.

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo arm	0.9% sodium chloride solution	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.
Ferric carboxymaltose arm	Ferric Carboxymaltose	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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 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
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

Trial Locations

Locations (1)

Policlinique Médicale Universitaire; 🇨🇭 Lausanne, Vaud, Switzerland