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

NCT03191201 | Terminated Phase 4 DMC

• 1 other identifier: 2016-01449
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Change from baseline in glucose homeostasis status, assessed by a dynamic two-step hyperglycaemic clamp investigation.

  two-step hyperglycaemic clamp investigation

  at 28 days of the injection of the Investigation Product

Secondary Outcomes (14)

• Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 14 days

  at 14 days of the injection of the Investigation Product

• Change from baseline in ultrasensitive C-reactive protein (hs-CRP) levels at 28 days

  at 28 days of the injection of the Investigation Product

• Change from baseline in interleukin-6 (IL-6) levels at 14 days

  at 14 days of the injection of the Investigation Product

• Change from baseline in interleukin-6 (IL-6) levels at 28 days

  at 28 days of the injection of the Investigation Product

• Change from baseline in adiponectin levels at 14 days

  at 14 days of the injection of the Investigation Product

Other Outcomes (2)

• Change from baseline in the plasma metabolomic profiling as assessed by metabolomics

  at 14 and 28 days of the injection of the Investigation Product

• Change from baseline in circulating miRNAs

  at 14 and 28 days of the injection of the Investigation Product

Study Arms (2)

Ferric carboxymaltose arm

ACTIVE COMPARATOR

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.

Drug: Ferric Carboxymaltose

Placebo arm

PLACEBO COMPARATOR

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.

Drug: 0.9% sodium chloride solution

Interventions

Ferric Carboxymaltose DRUG

Ferric Carboxymaltose 1000 mg iron element will be diluted in 250 mL of a commercially available sterile 0.9% sodium chloride solution.

Ferric carboxymaltose arm

0.9% sodium chloride solution DRUG

250 mL of a commercially available sterile 0.9% sodium chloride solution.

Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Age \<18 years.
• Menopause (defined as an amenorrhea of at least 12 months).
• 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.

Sponsors & Collaborators

• Prof Gérard WAEBER: lead
• Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator
• University of Lausanne: collaborator

Study Sites (1)

Policlinique Médicale Universitaire

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 35706490 DERIVED

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Glucose Metabolism Disorders; Metabolic Side Effects of Drugs and Substances

Interventions

ferric carboxymaltose; Sodium Chloride

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Gérard Waeber, MD

  Centre Hospitalier Universitaire Vaudois (CHUV)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: To ensure that patients are unaware of the study drug they are receiving, the infusion pouch will be prepared in a separate room by members of the pharmacy unit and opaque bags will cover the infusion kits and infusions will be done via dark coloured infusion sets. Finally, a curtain will be used to shield the injection site from the patient's view. To ensure that Outcomes Assessors are unaware of the study drug the patient is receiving, a seperate team of care providers will supervise the infusion of the investigation product and collect and/or manage adverse events (AEs) and serious adverse events (SAEs). The Outcome Assessor will not have access to participant related data during the randomised part of the study.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Department of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: May 17, 2017
• First Posted: June 19, 2017
• Study Start: June 21, 2017
• Primary Completion: March 9, 2020
• Study Completion: March 9, 2020
• Last Updated: March 26, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)