NCT01783106

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
59

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2014

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 31, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 4, 2013

Completed
12 months until next milestone

Study Start

First participant enrolled

February 1, 2014

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 18, 2019

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2019

Completed
Last Updated

October 31, 2019

Status Verified

October 1, 2019

Enrollment Period

5.2 years

First QC Date

January 31, 2013

Last Update Submit

October 29, 2019

Conditions

Crohn's Disease

Keywords

Crohn'santibioticshydroxychloroquineciprofloxacindoxycycline

Outcome Measures

Primary Outcomes (3)

  • • 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.

    Remission

    10 weeks

  • • Remission, defined as CDAI ≤150 maintained through to 24 weeks

    prolonged remission

    24 weeks

  • • Remission, defined as CDAI ≤150 maintained through to 52 weeks

    prolonged remission

    52 weeks

Secondary Outcomes (7)

  • • Remission defined as CDAI <150 at 4 weeks

    4 weeks

  • • Response defined as a fall in CDAI by >70 points at 4 weeks and 10 weeks

    4 weeks and 10 weeks

  • • Markers of cost (days admitted to hospital, days unable to carry out normal daily activities, need for surgery)

    52 weeks

  • • Quality of life at 4 weeks, at 10 weeks, or Early Withdrawal

    4 weeks and 10 weeks

  • • Patient global assessment of symptom severity by 10 cm visual analogue score at 4 weeks, at 10 weeks, or Early Withdrawal

    4 weeks and 10 weeks

  • +2 more secondary outcomes

Study Arms (2)

budesonide

ACTIVE COMPARATOR

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

Ciprofloxacine, doxycycline and hydroxychloroquine

EXPERIMENTAL

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: CiprofloxacinDrug: DoxycyclineDrug: Hydroxychloroquine

Interventions

CiprofloxacinDRUG

experimental

Ciprofloxacine, doxycycline and hydroxychloroquine
DoxycyclineDRUG

experimental

Ciprofloxacine, doxycycline and hydroxychloroquine
HydroxychloroquineDRUG

oral

Ciprofloxacine, doxycycline and hydroxychloroquine
BudesonideDRUG

active comparator

Also known as: Enterocort CR
budesonide

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Royal Liverpool and Broadgreen Unversity Hospitals Trust

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Related Publications (1)

  • Rhodes JM, Subramanian S, Flanagan PK, Horgan GW, Martin K, Mansfield J, Parkes M, Hart A, Dallal H, Iqbal T, Butterworth J, Culshaw K, Probert C. Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease. Dig Dis Sci. 2021 Aug;66(8):2700-2711. doi: 10.1007/s10620-020-06477-y. Epub 2020 Jul 17.

    PMID: 32681228DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

CiprofloxacinDoxycyclineHydroxychloroquineBudesonide

Condition Hierarchy (Ancestors)

Inflammatory Bowel DiseasesGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones4-QuinolonesQuinolonesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsTetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsChloroquineAminoquinolinesPregnenedionesPregnenesPregnanesSteroidsFused-Ring Compounds

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

January 31, 2013

First Posted

February 4, 2013

Study Start

February 1, 2014

Primary Completion

April 18, 2019

Study Completion

September 30, 2019

Last Updated

October 31, 2019

Record last verified: 2019-10

Locations

GB(1)