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Antibiotics and Hydroxychloroquine in Crohn's (APRiCCOT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01783106
Recruitment Status : Completed
First Posted : February 4, 2013
Last Update Posted : October 31, 2019
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

Brief 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.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Ciprofloxacin Drug: Doxycycline Drug: Hydroxychloroquine Drug: Budesonide Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (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
Actual Study Start Date : February 1, 2014
Actual Primary Completion Date : April 18, 2019
Actual Study Completion Date : September 30, 2019

Arm Intervention/treatment
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

Drug: Doxycycline

Drug: Hydroxychloroquine

Primary Outcome Measures :
  1. • 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 ]

  2. • Remission, defined as CDAI ≤150 maintained through to 24 weeks [ Time Frame: 24 weeks ]
    prolonged remission

  3. • Remission, defined as CDAI ≤150 maintained through to 52 weeks [ Time Frame: 52 weeks ]
    prolonged remission

Secondary Outcome Measures :
  1. • Remission defined as CDAI <150 at 4 weeks [ Time Frame: 4 weeks ]

  2. • Response defined as a fall in CDAI by >70 points at 4 weeks and 10 weeks [ Time Frame: 4 weeks and 10 weeks ]

  3. • Markers of cost (days admitted to hospital, days unable to carry out normal daily activities, need for surgery) [ Time Frame: 52 weeks ]
    cost effectiveness

  4. • Quality of life at 4 weeks, at 10 weeks, or Early Withdrawal [ Time Frame: 4 weeks and 10 weeks ]
    Quality of life

  5. • 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 ]

  6. • 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 ]
    adverse event monitoring

  7. • Fall in Faecal Calprotectin [ Time Frame: 4 weeks, 10 weeks, 24 weeks, 52 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01783106

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United Kingdom
Royal Liverpool and Broadgreen Unversity Hospitals Trust
Liverpool, Merseyside, United Kingdom, L7 8XP
Sponsors and Collaborators
Royal Liverpool University Hospital
National Association for Colitis and Crohn's Disease
National Institute for Health Research, United Kingdom
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Jonathan Michael Rhodes, Professor of Medicine, Royal Liverpool University Hospital Identifier: NCT01783106    
Other Study ID Numbers: Royal_Liverpool
2008-001137-99 ( EudraCT Number )
First Posted: February 4, 2013    Key Record Dates
Last Update Posted: October 31, 2019
Last Verified: October 2019
Keywords provided by Jonathan Michael Rhodes, Royal Liverpool University Hospital:
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Anti-Bacterial Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors