Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis

NCT01524757 | Unknown

• 1 other identifier: NL3364409612
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 3

Brief Summary

Hereditary Hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload causing damage of different important organs like heart, liver, pancreas and joints. Complications and symptoms can regress by intensive treatment reducing the iron overload stores.Different genes have been identified playing a role in the pathophysiology of iron overload. A clinically important HFE gene mutation is the C282Y, located on chromosome 6. Phlebotomy is currently the standard therapy which consists of removal of 500 ml whole blood weekly, representing a loss of 250 mg iron. In naive patients between 20 to 100 phlebotomies are required to reduce the serum ferritine levels to 50 μg/L. Thereafter, a lifelong maintenance therapy of 3 to 6 phlebotomies yearly is needed. For absorption, dietary iron ( 70%) is reduced by gastric acid form the ferric (Fe3+) to the ferrous form (Fe2+). Recently, in an observational open study, Hutchinson et al. found that HH patients treated with proton pump inhibitors (PPI) needed fewer phlebotomies, resulting in a drop of 2.5 (SEM 0.25) to 0.5 (SEM 0.25) liter per year. Research question: The primary objective is to determine the effectiveness and cost effectiveness of PPI's compared to standard phlebotomy therapy in the prevention of iron overload in HH patients. Multi-center trial in two hospitals in the South of Limburg (Atrium medical Center, Maastricht university medical center ) and hospital in Belgium (University Hospital Gasthuisberg). The study will be conducted in randomised double blind manner. The follow up will be one year. Patients are randomized either for the group receiving a PPI or a placebo. Every 2 month the ferritin level is measured and decided if the patient need a phlebotomy (Ferritin \>100 µg/L).

Conditions

Hemochromatosis

Outcome Measures

Primary Outcomes (1)

• the total number of phlebotomies for the group taking PPI treatment compared to the group taking placebo will be the primary endpoint of the study.

  12 months

Secondary Outcomes (1)

• number of participants with side effects

  12 months

Study Arms (2)

pantoprazol

EXPERIMENTAL

Drug: Pantoprazole

placebo

PLACEBO COMPARATOR

Drug: Pantoprazole

Interventions

Pantoprazole DRUG

pantoprazole 40mg 1dd1; 12 months

pantoprazol; placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with hereditary hemochromatosis (HH), homozygous for C282Y, currently treated with phlebotomy as maintenance therapy for at least 12 months with ≥ 3 phlebotomies per year.
• Age: 18 years- 60 years and weight \> 50 kg.

You may not qualify if:

• Patients receiving other therapies such as chelating therapy or forced dietary regimen.
• Patients younger than 18 years.
• HH patients with excessive overweight (BMI \> 35).
• Patients who are mentally incapacitated.
• Women being pregnant or expecting/ planning to become pregnant during the one year period of the study.
• Patients with a malignancy.
• Patients already on PPI treatment.
• Patients who experienced side effects of PPI's.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Annadal stichting: collaborator

Study Sites (3)

University hospital Gasthuisberg

Leuven, Limburg, 3000, Belgium

Location

Atrium MC Parkstad

Heerlen, Limburg, 6440 AG, Netherlands

Location

Maastricht university medical center

Maastricht, Limburg, 6202AZ, Netherlands

Location

Related Publications (27)

• Hutchinson C, Geissler CA, Powell JJ, Bomford A. Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut. 2007 Sep;56(9):1291-5. doi: 10.1136/gut.2006.108613. Epub 2007 Mar 7.

  PMID: 17344278 BACKGROUND

• Adams P, Brissot P, Powell LW. EASL International Consensus Conference on Haemochromatosis. J Hepatol. 2000 Sep;33(3):485-504. doi: 10.1016/s0168-8278(01)80874-6. No abstract available.

  PMID: 11020008 BACKGROUND

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• Vanclooster A, van Deursen C, Jaspers R, Cassiman D, Koek G. Proton Pump Inhibitors Decrease Phlebotomy Need in HFE Hemochromatosis: Double-Blind Randomized Placebo-Controlled Trial. Gastroenterology. 2017 Sep;153(3):678-680.e2. doi: 10.1053/j.gastro.2017.06.006. Epub 2017 Jun 15.

  PMID: 28624580 DERIVED

MeSH Terms

Conditions

Hemochromatosis

Interventions

Pantoprazole

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Overload; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• G Koek, Dr

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

G Koek, dr

CONTACT

+31-43-3875021; gh.koek@mumc.nl

C Deursen Van, dr

CONTACT

31-45-5279639; c.vandeursen@atriummc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 2, 2012
• Study Start: March 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: February 2, 2012

Record last verified: 2012-01

Locations

NL (2); BE (1)