Clinical trial NCT03191201: A Double Blind Randomised Placebo-controlled Trial to Assess the Role of Iron Repletion in Glucose Homeostasis.
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Iron-deficiency
Iron Toxicity
Glucose Metabolism Disorders (Including Diabetes Mellitus)
Metabolic Side Effects of Drugs
Metabolic Disorder, Glucose
Safety Issues
Keywords: Metabolomics, Transcriptomics, Ironomics
Lead sponsor: University of Lausanne
Sponsor class: OTHER
Collaborators: name: Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
name: Centre Hospitalier Universitaire Vaudois
name: University of Lausanne
First posted: 2017-06-19
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind randomised placebo-controlled, parallel group comparative inferiority study with open-label extension divided in two parts:

* A first randomised and double-blind part in which FCM or placebo will be administered at baseline and post-baseline parameters assessed.
* A second non-randomised, non-blinded open-label extension part starting at the end of part 1, in which participants randomised to the placebo group will receive a FCM injection and post-baseline parameters assessed.
Primary purpose: OTHER

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change from baseline in glucose homeostasis status, assessed by a dynamic two-step hyperglycaemic clamp investigation.
timeFrame: at 28 days of the injection of the Investigation Product
Secondary outcomes:
measure: Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 14 days
timeFrame: at 14 days of the injection of the Investigation Product
measure: Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 28 days
timeFrame: at 28 days of the injection of the Investigation Product
measure: Change from baseline in interleukin-6 (IL-6) levels at 14 days
timeFrame: at 14 days of the injection of the Investigation Product
measure: Change from baseline in interleukin-6 (IL-6) levels at 28 days
timeFrame: at 28 days of the injection of the Investigation Product
measure: Change from baseline in adiponectin levels at 14 days
timeFrame: at 14 days of the injection of the Investigation Product
measure: Change from baseline in adiponectin levels at 28 days
timeFrame: at 28 days of the injection of the Investigation Product
measure: Change from baseline in interleukin-1beta levels at 14 days
timeFrame: at 14 days of the injection of the Investigation Product
measure: Change from baseline in interleukin-1beta levels at 28 days
timeFrame: at 28 days of the injection of the Investigation Product
measure: Change from baseline in blood pressure levels at 14 days
timeFrame: at 14 days of the injection of the Investigation Product
measure: Change from baseline in blood pressure levels at 28 days
timeFrame: at 28 days of the injection of the Investigation Product
measure: Change from baseline in the plasma lipid profile level at 14 days
timeFrame: at 14 days of the injection of the Investigation Product
measure: Change from baseline in the plasma lipid profile level at 28 days
timeFrame: at 28 days of the injection of the Investigation Product
measure: Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 14 days
timeFrame: at 14 days of the injection of the Investigation Product
measure: Change from baseline in the Homeostasis Model Assessment (HOMA-2) index at 28 days
timeFrame: at 28 days of the injection of the Investigation Product
Other outcomes:
measure: Change from baseline in the plasma metabolomic profiling as assessed by metabolomics
timeFrame: at 14 and 28 days of the injection of the Investigation Product
measure: Change from baseline in circulating miRNAs
timeFrame: at 14 and 28 days of the injection of the Investigation Product
Locations:
city: Lausanne
country: Switzerland
facility: Policlinique Médicale Universitaire
state: Vaud
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois (CHUV)
name: Gérard Waeber, MD
role: STUDY_DIRECTOR
References:
citation: Jaccard E, Seyssel K, Gouveia A, Vergely C, Baratali L, Gubelmann C, Froissart M, Favrat B, Marques-Vidal P, Tappy L, Waeber G. Effect of acute iron infusion on insulin secretion: A randomized, double-blind, placebo-controlled trial. EClinicalMedicine. 2022 May 6;48:101434. doi: 10.1016/j.eclinm.2022.101434. eCollection 2022 Jun.