Antibiotics and Hydroxychloroquine in Crohn's

• Status: Completed
• Trial end date: 2019-09-30
• Target enrollment: 0
• Participant gender: All

Summary

There is growing evidence that Crohn's disease may be caused by replication of bacteria, perhaps particularly E. coli, within macrophages (a specialized sort of white blood cell). Laboratory studies show that a combination of antibiotics that can penetrate macrophages (such as ciprofloxacin and doxycycline) together with the anti-malarial drug hydroxychloroquine (which makes the contents of macrophage vesicles more alkaline and helps them to kill intracellular bacteria) is particularly effective at killing the E. coli within macrophages.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Royal Liverpool University Hospital
• Collaborators: National Association for Colitis and Crohn's Disease; National Institute for Health Research, United Kingdom
• Treatments: Anti-Bacterial Agents; Antibiotics, Antitubercular; Budesonide; Ciprofloxacin; Doxycycline; Hydroxychloroquine

Criteria

Inclusion Criteria:

• Patient is willing to participate in the study and has signed the informed consent

• Patients aged 18 or over with Crohn's disease diagnosed by conventional clinical, radiological and histological criteria.

• Crohn's disease involving small bowel, colon or both.

• Active Crohn's disease: Crohn's Disease Activity Index (CDAI)> 220 and CRP>10mg/l.

• Patients receiving mesalazine (5ASA) must have had a stable dose for at least one month.

• Patients receiving Azathioprine, or Mercaptopurine (who will be separately stratified) must have had a stable dose for at least 3 months

• Women of child bearing potential must have a negative urine pregnancy test prior to the start of study medication

Exclusion Criteria:

• Patients under 18 or unable to give informed consent.

• Any antibiotic use within the previous 4 weeks

• Known sensitivity to Ciprofloxacin, Doxycycline, Hydroxychloroquine, or Budesonide

• Patients with a history of tendon disorders related to Fluoroquinoline administration

• Any change to immunosuppressive therapy (Azathioprine, or Mercaptopurine) within the previous 3 months.

• Use of Infliximab or Adalimumab (anti-TNF antibody) or methotrexate within the previous 3 months

• Concurrent use of systemic corticosteroids in excess of oral prednisolone 5 mgs/day or budesonide 3mg/day)

• Any change to medication for Crohn's disease in previous 4 weeks.

• Patients with complications requiring surgery (significant intestinal obstruction, perforation or abscess)

• CDAI >450

• Participation in other trials in the last 3 months.

• Serious intercurrent infection or other clinically important active disease (including renal and hepatic disease)

• Pregnant, post-partum (<3months) or breast feeding females

• Patients with abnormal visual acuity (that does not correct with glasses) or unexplained visual symptoms

• Women of Child Bearing Potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period (double barrier methods such as condoms or diaphragms with spermicidal gel or foam), and for up to 4 weeks after the study.

• Patients who need to continue to receive oral contraceptives (if unwilling to use double barrier methods), oral anticoagulants tricyclic antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, Sucralfate, or Cyclosporine