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Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis (He-ppi)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified January 2012 by Maastricht University Medical Center.
Recruitment status was:  Not yet recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01524757
First Posted: February 2, 2012
Last Update Posted: February 2, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Annadal stichting
Information provided by (Responsible Party):
Maastricht University Medical Center
  Purpose

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).


Condition Intervention
Hemochromatosis Drug: Pantoprazole

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • 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. [ Time Frame: 12 months ]

Secondary Outcome Measures:
  • number of participants with side effects [ Time Frame: 12 months ]

Estimated Enrollment: 48
Study Start Date: March 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pantoprazol Drug: Pantoprazole
pantoprazole 40mg 1dd1; 12 months
Placebo Comparator: placebo Drug: Pantoprazole
pantoprazole 40mg 1dd1; 12 months

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Ferritin level between 50-100 μg/L at start of the inclusion.
  • Age: 18 years- 60 years and weight > 50 kg.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01524757


Contacts
Contact: G Koek, dr +31-43-3875021 gh.koek@mumc.nl
Contact: C Deursen Van, dr 31-45-5279639 c.vandeursen@atriummc.nl

Locations
Belgium
University hospital Gasthuisberg Not yet recruiting
Leuven, Limburg, Belgium, 3000
Contact: David Cassiman, prof. dr.    +32 16344626    david.cassiman@uzleuven.be   
Principal Investigator: David Cassiman, prof. dr.         
Netherlands
Atrium MC Parkstad Not yet recruiting
Heerlen, Limburg, Netherlands, 6440 AG
Contact: Cees Deursen, dr    +31-45-5279639    c.vandeursen@atriummc.nl   
Contact: Reggy Jaspers, drs    +31-43-3875021    r.jaspers@Mumc.nl   
Principal Investigator: C Deursen, dr         
Maastricht university medical center Not yet recruiting
Maastricht, Limburg, Netherlands, 6202AZ
Contact: Reggy Jaspers, drs    +31-43-3875021    r.jaspers@mumc.nl   
Contact: Ger Koek, dr-    +31-43-3875021    gh.koek@mumc.nl   
Principal Investigator: Ger Koek, dr         
Sponsors and Collaborators
Maastricht University Medical Center
Annadal stichting
Investigators
Principal Investigator: G Koek, Dr Maastricht University Medical Center
  More Information

Publications:
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. Epub 2007 Mar 7.
Adams P, Brissot P, Powell LW. EASL International Consensus Conference on Haemochromatosis. J Hepatol. 2000 Sep;33(3):485-504. Review.
Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys Acta. 2006 Jul;1763(7):700-10. Epub 2006 May 27. Review.
van der Plas SM, Hansen BE, de Boer JB, Stijnen T, Passchier J, de Man RA, Schalm SW. Generic and disease-specific health related quality of life of liver patients with various aetiologies: a survey. Qual Life Res. 2007 Apr;16(3):375-88. Epub 2006 Nov 25.
European Association For The Study Of The Liver. EASL clinical practice guidelines for HFE hemochromatosis. J Hepatol. 2010 Jul;53(1):3-22. doi: 10.1016/j.jhep.2010.03.001. Epub 2010 Apr 18.
Jacobs EM, Meulendijks CF, Elving L, van der Wilt GJ, Swinkels DW. Impact of the introduction of a guideline on the targeted detection of hereditary haemochromatosis. Neth J Med. 2005 Jun;63(6):205-14.
Swinkels DW, Janssen MC, Bergmans J, Marx JJ. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches. Clin Chem. 2006 Jun;52(6):950-68. Epub 2006 Apr 20. Review.
Rombout-Sestrienkova E, Nieman FH, Essers BA, van Noord PA, Janssen MC, van Deursen CT, Bos LP, Rombout F, van den Braak R, de Leeuw PW, Koek GH. Erythrocytapheresis versus phlebotomy in the initial treatment of HFE hemochromatosis patients: results from a randomized trial. Transfusion. 2012 Mar;52(3):470-7. doi: 10.1111/j.1537-2995.2011.03292.x. Epub 2011 Aug 16.
Hungin AP, Rubin G, O'Flanagan H. Factors influencing compliance in long-term proton pump inhibitor therapy in general practice. Br J Gen Pract. 1999 Jun;49(443):463-4.
Hicken BL, Tucker DC, Barton JC. Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis. Am J Gastroenterol. 2003 Sep;98(9):2072-7.
Bonapace ES, Fisher RS, Parkman HP. Does fasting serum gastrin predict gastric acid suppression in patients on proton-pump inhibitors? Dig Dis Sci. 2000 Jan;45(1):34-9.
Newman BH. Blood donor complications after whole-blood donation. Curr Opin Hematol. 2004 Sep;11(5):339-45. Review.
HOFSTETTER JR. [Risks in blood-letting in therapy of hemochromatosis]. Gastroenterologia. 1957;87(3-4):186-91. French.
Klinkenberg-Knol EC, Festen HP, Jansen JB, Lamers CB, Nelis F, Snel P, Lückers A, Dekkers CP, Havu N, Meuwissen SG. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med. 1994 Aug 1;121(3):161-7.
Klinkenberg-Knol EC, Nelis F, Dent J, Snel P, Mitchell B, Prichard P, Lloyd D, Havu N, Frame MH, Romàn J, Walan A; Long-Term Study Group. Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa. Gastroenterology. 2000 Apr;118(4):661-9.
Creutzfeldt W, Lamberts R. Is hypergastrinaemia dangerous to man? Scand J Gastroenterol Suppl. 1991;180:179-91. Review.
Solcia E, Fiocca R, Havu N, Dalväg A, Carlsson R. Gastric endocrine cells and gastritis in patients receiving long-term omeprazole treatment. Digestion. 1992;51 Suppl 1:82-92.
Lamberts R, Brunner G, Solcia E. Effects of very long (up to 10 years) proton pump blockade on human gastric mucosa. Digestion. 2001;64(4):205-13.
Hallerbäck B, Unge P, Carling L, Edwin B, Glise H, Havu N, Lyrenäs E, Lundberg K. Omeprazole or ranitidine in long-term treatment of reflux esophagitis. The Scandinavian Clinics for United Research Group. Gastroenterology. 1994 Nov;107(5):1305-11.
Lamberts R, Creutzfeldt W, Strüber HG, Brunner G, Solcia E. Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis. Gastroenterology. 1993 May;104(5):1356-70.
Sharma BK, Santana IA, Wood EC, Walt RP, Pereira M, Noone P, Smith PL, Walters CL, Pounder RE. Intragastric bacterial activity and nitrosation before, during, and after treatment with omeprazole. Br Med J (Clin Res Ed). 1984 Sep 22;289(6447):717-9.
Fried M, Siegrist H, Frei R, Froehlich F, Duroux P, Thorens J, Blum A, Bille J, Gonvers JJ, Gyr K. Duodenal bacterial overgrowth during treatment in outpatients with omeprazole. Gut. 1994 Jan;35(1):23-6.
Verdu E, Viani F, Armstrong D, Fraser R, Siegrist HH, Pignatelli B, Idström JP, Cederberg C, Blum AL, Fried M. Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso compounds. Gut. 1994 Apr;35(4):455-60.
Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004 Oct 27;292(16):1955-60.
Koop H, Bachem MG. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol. 1992 Jun;14(4):288-92.
Termanini B, Gibril F, Sutliff VE, Yu F, Venzon DJ, Jensen RT. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med. 1998 May;104(5):422-30.

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01524757     History of Changes
Other Study ID Numbers: NL3364409612
First Submitted: January 31, 2012
First Posted: February 2, 2012
Last Update Posted: February 2, 2012
Last Verified: January 2012

Additional relevant MeSH terms:
Hemochromatosis
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Iron Overload
Iron Metabolism Disorders
Metabolic Diseases
Pantoprazole
Proton Pump Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action


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