Title: Antioxidants and magnesium for the treatment of pain in hereditary and idiopathic chronic pancreatitis
Funder: Department of Health and Social Care

Abstract: Background Chronic pancreatitis (CP) is responsible for significant morbidity, but no medical treatments which have been proven to modify disease progression. Antioxidants and micronutrient supplementation have the potential to reduce attacks of pain in CP, and hence the burden both on the individual patient and on the health services in general, and have been used for many years to reduce attacks of pain in CP, but without any good randomised trial evidence to support their use. We propose the first large randomised controlled trial of the use of antioxidants and magnesium in reducing pain from chronic pancreatitis. Aims Using patients with Hereditary Chronic Pancreatitis (HP) registered with the European Registry for Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) or patients with Idiopathic Chronic Pancreatitis (ICP) recruited from specialist pancreatic clinics as a model for all types of CP we aim to investigate the efficacy of antioxidants and magnesium in reducing the number or severity of attacks of pain in CP. We will also assess the impact of the treatment on the patients’ overall quality of life. Plan of Investigation A total of 240 patients between the ages of 5 and 65 with documented CP (either HP or ICP) will be recruited from the UK and Europe by two principle randomisation centres, Liverpool and Greifswald. (NB, the Greifswald centre is funded separately and has already recruited 40 patients; we anticipate 150 UK patients.) Patients will be randomised to one of three groups. The groups will receive antioxidant medication, magnesium or placebo in order to compare pancreatic pain over a twelve month period. Symptoms will be recorded using weekly pain diaries and 12-weekly quality of life questionnaires. At 12-weekly intervals urine and stool samples will be taken for analysis of medication compliance and to assess for evidence of pancreatic inflammation. Potential Impact Chronic pancreatitis is common, with an incidence of about 10 new cases per 100,000 population per year, and a prevalence of 30 cases per 100,000. In the UK there were 7,602 admissions to hospital for acute pancreatitis and 2,049 admissions for chronic pancreatitis in 1989/1990, for both conditions the incidence is increasing such that there were 11,373 and 3,065 admissions in 1999/2000. In a study of 176 patients with Hereditary Pancreatitis in the EUROPAC registry there were an average of 2.84 attacks of pancreatitis per year, each lasting on average 5.45 days. Antioxidants and/or magnesium therapy have the potential to significantly reduce the frequency and/or severity of attacks of pancreatitis, and hence both the burden on the individual patient and on the health services.

Lay abstract: Chronic pancreatitis causes significant pain and is increasingly common, however there is no good treatment proven to reduce attacks of pain. Previous evidence for the usefulness of micronutrient antioxidant therapy in recurrent pancreatitis has been suggestive but inconclusive. The usefulness of magnesium-therapy has been demonstrated only in an animal model of acute pancreatitis where it reduced the premature activation of digestive proteases in the pancreas and had a beneficial effect on the course of experimental pancreatitis. Most pancreatitis is alcohol related but studies involving alcoholic patients are notoriously difficult to draw conclusions from. The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) is coordinated from Liverpool and represents the worlds largest registry of non-alcohol related pancreatitis. Patients on the registry are a highly committed group. The objectives of this study are to determine the efficacy of antioxidant medication (ANTOX) and magnesium (Magnesiocard) compared to placebo in the treatment of pain in patients with pancreatitis using hereditary pancreatitis (HP) and idiopathic chronic pancreatitis (ICP) as models. 240 patients (150 in UK) between the ages of 5 and 65 years will be recruited from within EUROPAC and from specialist clinics. Patients will be randomised to receive ANTOX, magnesiocard or placebo. At 12 weekly intervals quality of life will be assessed using the SF-36 questionnaire for adults, and the PEDS quality of life score for children. Magnesium, antioxidant status and inflammatory markers will be measured in urine and faecal elastase in stool. The primary outcome of the trial will be a reduction in the number of days of pain, adults will complete the McGill pain questionnaire, whilst children will complete the paediatric pain questionnaire. Parents of affected children will complete a similar proxy questionnaire. Pain parameters will be recorded using weekly pain diaries.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL