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

Hemochromatosis Clinical Trial

— He-ppi  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01524757
• Other study ID #: NL3364409612
• Status: Not yet recruiting
• Phase: N/A
• First received: January 31, 2012
• Last updated: February 1, 2012
• Start date: March 2012
• Est. completion date: August 2013

Study information

• Verified date: January 2012
• Source: Maastricht University Medical Center
• Contact: G Koek, dr
• Phone: +31-43-3875021
• Email: gh.koek[@]mumc.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemochromatosis

Intervention

Drug:
• Pantoprazole
pantoprazole 40mg 1dd1; 12 months

Locations

Country	Name	City	State
Belgium	University hospital Gasthuisberg	Leuven	Limburg
Netherlands	Atrium MC Parkstad	Heerlen	Limburg
Netherlands	Maastricht university medical center	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Annadal stichting

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (26)

Adams P, Brissot P, Powell LW. EASL International Consensus Conference on Haemochromatosis. J Hepatol. 2000 Sep;33(3):485-504. Review. — View Citation

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. — View Citation

Creutzfeldt W, Lamberts R. Is hypergastrinaemia dangerous to man? Scand J Gastroenterol Suppl. 1991;180:179-91. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

HOFSTETTER JR. [Risks in blood-letting in therapy of hemochromatosis]. Gastroenterologia. 1957;87(3-4):186-91. French. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Koop H, Bachem MG. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol. 1992 Jun;14(4):288-92. — View Citation

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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. — View Citation

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. — View Citation

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Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys Acta. 2006 Jul;1763(7):700-10. Epub 2006 May 27. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	number of participants with side effects		12 months	Yes