Antibiotics and Hydroxychloroquine in Crohn's (APRiCCOT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Royal Liverpool University Hospital
Sponsor:
Collaborators:
National Association for Colitis and Crohn's Disease
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Jonathan Michael Rhodes, Royal Liverpool University Hospital
ClinicalTrials.gov Identifier:
NCT01783106
First received: January 31, 2013
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Crohn's Disease
Drug: Ciprofloxacin
Drug: Doxycycline
Drug: Hydroxychloroquine
Drug: Budesonide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Randomised Study to Compare Combination Antibiotic Therapy (Ciprofloxacin, Doxycycline and Hydroxychloroquine) With Standard Therapy (Budesonide) in the Treatment of Active Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Royal Liverpool University Hospital:

Primary Outcome Measures:
  • • Remission, defined as Crohn's Disease activity index (CDAI) <150 at 10 weeks without addition of any other medication or treatment for the Crohn's Disease. [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Remission

  • • Remission, defined as CDAI ≤150 maintained through to 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    prolonged remission

  • • Remission, defined as CDAI ≤150 maintained through to 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    prolonged remission


Secondary Outcome Measures:
  • • Remission defined as CDAI <150 at 4 weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    remission

  • • Response defined as a fall in CDAI by >70 points at 4 weeks and 10 weeks [ Time Frame: 4 weeks and 10 weeks ] [ Designated as safety issue: No ]
    response

  • • Markers of cost (days admitted to hospital, days unable to carry out normal daily activities, need for surgery) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    cost effectiveness

  • • Quality of life at 4 weeks, at 10 weeks, or Early Withdrawal [ Time Frame: 4 weeks and 10 weeks ] [ Designated as safety issue: No ]
    Quality of life

  • • Patient global assessment of symptom severity by 10 cm visual analogue score at 4 weeks, at 10 weeks, or Early Withdrawal [ Time Frame: 4 weeks and 10 weeks ] [ Designated as safety issue: No ]
    efficacy

  • • Adverse Events and possible drug-related side effects: nausea, diarrhoea, mood disturbance, sleep disturbance - will all be assessed at each visit [ Time Frame: throughout 12 month follow-up ] [ Designated as safety issue: Yes ]
    adverse event monitoring

  • • Fall in Faecal Calprotectin [ Time Frame: 4 weeks, 10 weeks, 24 weeks, 52 weeks ] [ Designated as safety issue: No ]
    efficacy


Estimated Enrollment: 100
Study Start Date: January 2013
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: budesonide
Oral Budesonide 9mg per day for 8 weeks followed by 6mg per day for 2 weeks and subsequent 3mg per day over a further 2 weeks
Drug: Budesonide
active comparator
Other Name: Enterocort CR
Experimental: Ciprofloxacine, doxycycline and hydroxychloroquine
Oral Ciprofloxacin 500mg bd plus Doxycycline 100mg bd and Hydroxychloroquine 200mg tds followed by a further 20 weeks continued therapy with Doxycycline 100mg bd and Hydroxychloroquine 200mg tds
Drug: Ciprofloxacin
experimental
Drug: Doxycycline
experimental
Drug: Hydroxychloroquine
oral

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01783106

Locations
United Kingdom
Royal Liverpool and Broadgreen Unversity Hospitals Trust Recruiting
Liverpool, Merseyside, United Kingdom, L7 8XP
Contact: Kate Martin, SRN    0151 706 4074    kate.martin@rluhbt.nhs.uk   
Sub-Investigator: Jonathan M Rhodes, MD         
Principal Investigator: Sreedar Subramanian, MD         
Sponsors and Collaborators
Royal Liverpool University Hospital
National Association for Colitis and Crohn's Disease
National Institute for Health Research, United Kingdom
  More Information

No publications provided

Responsible Party: Jonathan Michael Rhodes, Professor of Medicine, Royal Liverpool University Hospital
ClinicalTrials.gov Identifier: NCT01783106     History of Changes
Other Study ID Numbers: Royal_Liverpool, 2008-001137-99
Study First Received: January 31, 2013
Last Updated: June 26, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Royal Liverpool University Hospital:
Crohn's
antibiotics
hydroxychloroquine
ciprofloxacin
doxycycline

Additional relevant MeSH terms:
Crohn Disease
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Anti-Bacterial Agents
Antibiotics, Antitubercular
Budesonide
Ciprofloxacin
Doxycycline
Hydroxychloroquine
Anti-Asthmatic Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antimalarials
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Antitubercular Agents
Autonomic Agents
Bronchodilator Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 21, 2014