The aim of this preliminary study is to prospectively assess the efficacy of LDN as induction therapy in CD.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Endoscopic remission at week 12 defined as SES-CD <=2 and ulcerated surface
subscore <=1 in all five segments.
Secondary outcome
• Proportion of patients in steroid free clinical remission defined as a by an
HBI score of <=4 and complete tapering of systemic corticosteroids and
endoscopic remission at week 12
• Response defined by a decrease in HBI of >=3 points compared to baseline and
endoscopic response defined as a reduction of SES-CD score by >=50% vs baseline
at week 12
• Changes in laboratory measures of inflammation (CRP, fecal calprotectin) from
baseline at week 12,24 and 52
• Adverse events at every visit
• Quality of life, via the disease specific and validated sIBDQ at screening,
week 4, 12, 24 and 52
• Fatigue, via the FACIT-F and MFI at screening, week 4, 12, 24 and 52
• Anxiety, Depression, Sleepdisturbance, via the PROMIS NIH at screening,
week 4, 12, 24 and 52
• Healthcare costs and utilization, via WPAI and EQ5D at screening, week 4, 12,
24 and 52
• PROM, via the IBD validated PRO2-tool (at screening, week 2, 4, 8, 12, 24 and
52)
• Proportion of patients in corticosteroid free clinical remission at week 24
and 52
• Response (HBI) at week 24 and 52
• Endoscopic remission and response at week 52
• Anxiety, Depression, Sleepdisturbance, via the PROMIS NIH at screening,
week 4, 12, 24 and 52
Background summary
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, which
includes Crohn*s disease (CD) and ulcerative colitis (UC). Several drugs exist
to induce and maintain remission, and these drugs are usually prescribed in a
step up fashion. In contrast to UC, for patients with CD after induction of
remission with corticosteroids, maintenance of remission is only achieved with
immunosuppressive drugs, mainly thiopurines. Although these drugs are effective
in 60% for remaining clinical remission after 12 months, the drawback of these
drugs are the side effects that include bone marrow suppression, liver test
abnormalities and malignancies. Pilot studies in patients with CD showed a
positive effect of low dose naltrexone (LDN) therapy, with 15 of 17 patients
showing a clinical response. A subsequent randomized, placebo-controlled,
double blind study in 34 patients found a response rate of 88% in the LDN group
versus 40% in the placebo group after 12 weeks of therapy. In addition LDN was
also shown to be safe in pediatric IBD patients, and resulted in significantly
reduced PCDAI scores, with 25% of patients achieving remission and 67% showing
improvement of disease.(1-4)
Study objective
The aim of this preliminary study is to prospectively assess the efficacy of
LDN as induction therapy in CD.
Study design
This is a multicentre, prospective, randomized, placebo-controlled study.
Patients with mild to moderate active CD will be randomized 1:1 to receive
treatment with either LDN 4.5 mg or placebo for 12 weeks. After week 12
patients will be invited to participate in an open label exploratory extension
study with visits at week 24, 26 and 52.
Intervention
LDN induction therapy 4.5 mg once daily or placebo orally for 12 weeks followed
by open label maintenance therapy of 4.5 mg LDN once daily during one year.
Study burden and risks
Patients participating in this study will come to their habitual check-ups at
the department of Gastroenterology and Hepatology. As additional burden, they
will undergo a colonoscopy during screening and at week 12 and will be asked to
fill out questionnaires during visits and telephone calls. During the visits
blood samples and fecal samples will be collected as normal follow-up of
patients with an active disease. Telephone interviews are planned at
randomization, week 2 and week 6. During these calls the patients reported
outcomes and clinical disease activity (HBI) will be recorded. Benefits of the
proposed therapy are the anti-inflammatory effects on CD disease activity. This
study will have direct impact on the management of IBD patients by determining
if LDN is involved in the treatment of mild to moderate Crohn*s disease. If LDN
is possible to induce remission, this drug might be regarded as a first line
therapy after failure of conventional treatment in the treatment of active CD
because of the oral administration and anticipated low frequency of side
effects.
Doctor Molewaterplein 40
Rotterdam 3015 GD
NL
Doctor Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• Age 18 or older; must have the ability to understand and sign a written ICF
• Diagnosis of Crohn*s disease >=3 months before screening.
• Objective evidence of inflammation at baseline as defined by endoscopy with
mucosal ulcers in the ileum or colon or both, and a SES-CD score of 3-15.
• Concurrent therapies with stable doses of azathioprine, mercaptopurine, MTX
or steroids
Exclusion criteria
• Current use of i.v. corticosteroids.
• Imminent need for in-hospital treatment.
• Pregnancy or lactation.
• Current treatment with investigational drug; current or past treatment within
3 months prior to randomization with a biological agent.
• Stool sample positive for Clostridium difficile (C. diff) toxin, pathogenic
Escherichia coli (E. coli), Salmonella species (spp), Shigella spp,
Campylobacter spp, or Yersinia spp.
• Other significant illnesses that may interfere with the study, stricture
causing obstructive symptoms, or fistulising disease complicated by infection.
• Opiates use or drugs and/or alcohol abuse.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-000852-32-NL |
| CCMO | NL69149.078.19 |