This is a multi-centre randomised phase III, double blind, placebo controlled, parallel group, outpatient study in patients diagnosed with Hereditary Pancreatitis and Idiopathic Chronic Pancreatitis.

The hypothesis to be tested is a 30% reduction in the number of days due to pancreatitis from 12.5 days per year to less than nine days per year under the treatment with Magnesium or an antioxidant cocktail called ANTOX.

A total of 240 patients will be randomised to one of three treatment groups in order to compare pancreatic pain over a twelve month period.

Condition	Intervention	Phase
Hereditary Pancreatitis and idiopathic chronic pancreatitis	Drug: Magnesium (15 mmol/d) and ANTOX vers. 1.2 (300 µg organic selenium, 54000 IU beta carotene, 750 mg vitamin C, 540 IU vitamin E, 2700 mg methionine)	Phase II Phase III

Further Study Details: 

Primary Outcomes: Reduction in the number of days of pancreatic pain during 12 continuous months of treatment.
Secondary Outcomes: Disruption of activities of normal living.; Analgesic use for pancreatic pain.; Number of days of hospitalisation for conditions related to pancreatitis.; Quality of Life (QoL) measures.; Markers of inflammatory response and activity of the pancreas.; Changes in urinary levels of magnesium, selenium and vitamin C over the duration of the study.; Antioxidant response as measured by urinary thiobarituric acid levels.; Response in patients with Hereditary Pancreatitis and Idiopathic Chronic Pancreatitis.; Correlate response with gene mutations underlying Hereditary Pancreatitis (PRSS1, other) and Idiopathic Chronic Pancreatitis (SPINK1, CFTR, other).; Data acquisition including makers of inflammatory response during acute attack of chronic pancreatitis.
Expected Total Enrollment:  240

Title: EUROPAC 2 trial to investigate the efficacy of ANTOX (vers)1.2 and MGCT Magnesiocard) for the treatment of Hereditary Pancreatitis and idiopathic chronic pancreatitis Study drug: ANTOX (vers)1.2 MGCT (Magnesiocard) Intended indication:Hereditary Pancreatitis and idiopathic chronic pancreatitis Study design:A multi-centre, double blind, and placebo-controlled, randomised, parallel group study Patient population: Patients with Hereditary Pancreatitis or Idiopathic Chronic Pancreatitis Number of patients: Total of 240 patients in three equal groups Proposed number of initial centres: two (Greifswald, Germany and Liverpool, UK).

Duration of dosing: 12 months Treatment groups: Group one: two ANTOX (vers)1.2 tablet, three times daily, Antioxidant treatment: daily: 300 µg organic selenium, 54000 IU beta carotene = 18 mg, 750 mg vitamin C, 540 IU of vitamin E = 240 mg, 2700 mg methionine.

Group two: two Magnesium-L-Aspartate-hydrochloride (MGCT) (Magnesiocard  2,5 mmol tablets three times a day, total dose 15 mmol ( 365 mg/ per day) tablets.

Group three: The same number of tablets as in Groups one and two but placebo instead of active drug.

Efficacy parameters: Primary: Pain (number of days of pancreatic pain) Secondary: Severity of pain; analgesic use for pancreatic pain; number of days of hospitalisation for conditions related to chronic pancreatitis; Quality of Life; markers of inflammatory response, antioxidant response, changes in urinary levels of magnesium, selenium, vitamin C and activity of the pancreatitis and pancreatic function.

Safety Parameters: Toxicity; Adverse Events

Ages Eligible for Study:  5 Years   -   40 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Patients must have had pancreatitis diagnosed for at least one year.
2. Patients must be willing to be followed up regularly for at least one year.
3. Patients aged five to 40 years of age.
4. Individuals must have characteristic pancreatic pain that is either intermittent or continuous.

Exclusion Criteria:

1. Patients that do not consent to be involved in the trial, or whose parents do not consent for their children to be involved.
2. Patients or guardians of underage patients, with learning disabilities or other cognitive or sensory impairments that would prevent adequate understanding of the study requirements.
3. Patients who have had treatment <3months, or are currently receiving treatment with antioxidants or magnesium tablets.
4. Patients who have had recent (<3months), or are currently receiving treatment with oral hypoglycaemics or steroid treatment.
5. Patients with renal failure (serum creatinine  200 g/l).
6. Patients with atrio-ventricular-block.
7. Serum triglyceride levels  1000 mg/dl.
8. Patients under the age of five years or over the age of 40 years.
9. Patients who are dependent on daily opiate analgesia (morphine or equivalent) for more than 12 months.
10. Patients who have chronic hepatic failure, or serious impairment of pulmonary, cardiac, neurological or cerebral function.
11. Patients who are participating in another drug trial.
12. Patients who are pregnant.
13. Women of childbearing age who are not using contraception.
14. Lactating mothers.
15. Any disorder that would prevent adequate absorption of the active treatment.

Please refer to this study by ClinicalTrials.gov identifier  NCT00142233

Markus M Lerch, Professor of Medicine      03834-86  Ext. 7230    lerch@uni-greifswald.de
Julia V Mayerle, MD      03834-86  Ext. 7244    mayerle@uni-greifswald.de

Germany, Baden-Würtemberg
      Department of Visceral and Tramsplant Surgery, Ruprecht-Karls-Universität Heidelberg, Heidelberg,  Baden-Würtemberg,  Germany; Recruiting

Study chairs or principal investigators

Markus M Lerch, Professor of Medicine,  Principal Investigator,  Department of Gastroenterology, Endocrinology and Nutrition, Ernst-Moritz-Arndt University Greifswald   
Julia V Mayerle, MD,  Principal Investigator,  Department of Gastroenterology, Endocrinology and Nutrition, Ernst-Moritz-Arndt University Greifswald   
John P Neoptolemos, Professor of Surgery,  Principal Investigator,  Department of Surgery, University of Liverpool   

Study ID Numbers:  EUROPAC-2
Last Updated:  September 1, 2005
Record first received:  August 31, 2005
ClinicalTrials.gov Identifier:  NCT00142233
Health Authority: Germany: Federal Institute for Drugs and Medicinal Devices
ClinicalTrials.gov processed this record on 2005-09-06