Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis
Overview[ - collapse ][ - ]
| 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). |
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| Condition | Hemochromatosis |
| Intervention | Drug: Pantoprazole |
| Phase | N/A |
| Sponsor | Maastricht University Medical Center |
| Responsible Party | Maastricht University Medical Center |
| ClinicalTrials.gov Identifier | NCT01524757 |
| First Received | January 31, 2012 |
| Last Updated | February 1, 2012 |
| Last verified | January 2012 |
Tracking Information[ + expand ][ + ]
| First Received Date | January 31, 2012 |
|---|---|
| Last Updated Date | February 1, 2012 |
| Start Date | March 2012 |
| Estimated Primary Completion Date | August 2013 |
| Current 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] [Designated as safety issue: Yes] |
| Current Secondary Outcome Measures | number of participants with side effects [Time Frame: 12 months] [Designated as safety issue: Yes] |
Descriptive Information[ + expand ][ + ]
| Brief Title | Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis |
|---|---|
| Official Title | Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis |
| 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). |
| Detailed Description | Not Provided |
| Study Type | Interventional |
| Study Phase | N/A |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition | Hemochromatosis |
| Intervention | Drug: Pantoprazole pantoprazole 40mg 1dd1; 12 months |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Not yet recruiting |
|---|---|
| Estimated Enrollment | 48 |
| Estimated Completion Date | August 2013 |
| Estimated Primary Completion Date | August 2013 |
| Eligibility 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. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: G Koek, dr +31-43-3875021 gh.koek@mumc.nl |
| Location Countries | Belgium, Netherlands |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01524757 |
|---|---|
| Other Study ID Numbers | NL3364409612 |
| Has Data Monitoring Committee | No |
| Information Provided By | Maastricht University Medical Center |
| Study Sponsor | Maastricht University Medical Center |
| Collaborators | Annadal stichting |
| Investigators | Principal Investigator: G Koek, Dr Maastricht University Medical Center |
| Verification Date | January 2012 |
Locations[ + expand ][ + ]
| University hospital Gasthuisberg | Leuven, Limburg, Belgium, 3000 Contact: David Cassiman, prof. dr. | +32 16344626 | david.cassiman@uzleuven.bePrincipal Investigator: David Cassiman, prof. dr. Not yet recruiting |
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| Atrium MC Parkstad | Heerlen, Limburg, Netherlands, 6440 AG Contact: Cees Deursen, dr | +31-45-5279639 | c.vandeursen@atriummc.nlPrincipal Investigator: C Deursen, dr Not yet recruiting |
| Maastricht university medical center | Maastricht, Limburg, Netherlands, 6202AZ Contact: Reggy Jaspers, drs | +31-43-3875021 | r.jaspers@mumc.nlPrincipal Investigator: Ger Koek, dr Not yet recruiting |