InflammationPhase 2LDNNCT00663117
The Effects of Naltrexone on Active Crohn's Disease
A Phase 2 study testing Naltrexone-HCl in people with Inflammation and Crohn's Disease, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
It is hypothesized that the opioid antagonist naltrexone will improve inflammation of the bowel and quality of life in subjects with active Crohn's disease compared to placebo. In order to test this hypothesis the following specific aims are proposed: 1. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Inflammation, Crohn's Disease
- What is being tested?
- Naltrexone-HCl
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2006to Oct 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All subjects must give written informed consent
- Male or female subjects, > 18 years
- Patients must have endoscopic, histologic, or radiographic confirmed Crohn's Disease.
- Patients must have a Crohn's Disease Activity Index (CDAI) of at least 220 at Baseline
- Stable doses of medications for Crohn's disease over proceeding 4 weeks (for aminosalicylates and steroids: prednisone of 10mg or less daily and Entocort 3 mg/ day are allowed), and 12 weeks for azathioprine or 6-mercaptopurine.)
Who cannot join
- Subjects with ostomies or ileorectal anastomosis from prior surgical colectomy.
- Subjects who received infliximab (Remicade) within 8 weeks of study screening or humira for 4 weeks.
- Subjects requiring steroids either intravenously or prednisone >10mg /day or Entocort > 3 mg daily.
- Subjects with short-bowel syndrome.
- Abnormal liver enzymes at screening visit or known hepatitis or cirrhosis
- Hemoglobin less than 10.
Show all 9Show fewer
- Subjects with cancer (other than skin cancer) in past 5 years.
- Women of childbearing potential unless surgically sterile or using adequate contraception (either IUD, oral or deport contraceptive, or barrier plus spermicide), and willing and able to continue contraception for 3 months after the completion of the study.
- Women who are pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: The Effects of Naltrexone in Active Crohn's Disease
It is hypothesized that the opioid antagonist naltrexone will improve inflammation of the bowel and quality of life in subjects with active Crohn's disease compared to placebo. In order to test this hypothesis the following specific aims are proposed:
- Evaluate the effects of low dose naltrexone compared to placebo on the activity of Crohn's disease by the following end points: Crohn's Disease Activity Index (CDAI), pain assessment, laboratory values (CRP and ESR), endoscopic appearance, histology, and quality of life surveys;
- Examine the effects of naltrexone given over 3 months compared to 6 months for durability of response;
- Determine the safety and toxicity of low dose naltrexone in subjects with active Crohn's disease, and
- Study the mechanism by which naltrexone exerts its effect by measuring plasma enkephalin levels of subjects on therapy.
Purpose statement: The purpose of this study is to evaluate the effects of low dose naltrexone in a blinded placebo controlled study to determine the safety and efficacy of this compound in those with active Crohn's disease.
Read the detailed description
Study design : The study is designed as a double-blind placebo controlled study for 3 months followed by a pseudo cross-over such that all subjects receiving placebo the first 3 months will receive active drug the second 3 months and all receiving naltrexone the first 3 months remain on the drug the last 3 months of this 6 month study.
- Conditions
- Inflammation, Crohn's Disease
- Being tested
- Naltrexone-HCl, Placebo
- Keywords
- naltrexone, LDN, IBD, Inflammatory bowel disease
- Medical subject headings
- Inflammation, Crohn Disease, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naltrexone-HClDrug
Also called LDN, Revia
naltrexone 4.5 mg
PlaceboDrug
Also called sugar pill
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo, Sugar pill | Placebo comparator | placebo for 3 months blinded then followed by an open-labelled study and all are treated with naltrexone 4.5 mg for 3 additional months Receives: Drug: Naltrexone-HCl; Drug: Placebo |
| Naltrexone-HCl | Active comparator | Subjects are treated in a blinded fashion for 3 months with naltrexone 4.5 mg po for active Crohn's disease followed an open-labelled study where naltrexone is given an additional 3 months at 4.5 mg po; hence the total treatment interval in this arm is 6 months. The response to the intervention administered is measured in the activity index and mucosal healing by colonoscopy. Receives: Drug: Naltrexone-HCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;
The CDAI score is a number which consists of information collected from a 7-day diary from the patient regarding symptoms. It also includes objective information from the physical exam, weight and hemotocrit. Remission is considered a score of 150 or less. Active disease is considered 220 or greater. A response to therapy is considered a decline in the CDAI score of 70-points from baseline.
Measured: 3 months
Secondary outcomes (3)
Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)
IBDQ (Inflammatory bowel Disease questionnaire) contains questions about health ranging from a score of poor (i.e., 32) to excellent (i.e., 224) an increase from baseline indicates improvement in quality of life.
Measured: Between baseline and 3 months
Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy
A secondary outcome was the appearance of the colonic mucosa on endoscopy using the Crohn's Disease Endoscopic Index of Severity (CDEIS) score described by Mary et al. Gut 1989;30:983-989.This score ranges from 0-44 based upon the extent and severity of inflammation and ulcers seen during endoscopy of the colon. A response is a drop of > 5 points from baseline. Endoscopic remission is a score of < 6 and Complete endoscopic remission is a score of > 3.
Measured: 12 weeks
Histology Inflammatory Score by Colon Biopsies
Histology scores to assess microscopic inflammation and structural architecture were determined at baseline and after 12 weeks of either naltrexone therapy or placebo by mucosal biopsy samples obtained during colonoscopies.The pathology specimens were reviewed and scored by a Pathologist blinded to the treatment. The mean scores at baseline were the same between both groups.Differences between naltrexone and placebo treated subjects was assessed.The range in scores could be 0-25, with 0 representing no inflammation and 25 being maximum or severe inflammation..
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2008 (estimated)
- Study startSep 2006
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Broad Foundation
- Responsible party
- Sponsor
- Investigators
- Jill P. Smith, M.D., Principal investigator, Pennsylvania State University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00663117
- Sponsor's protocol ID
- DK073614 l
- Other IDs
- 1R03DK073614, IBD-0180R
- Acronym
- LDN
- Status last verified
- May 2013
- First submitted
- 18 Apr 2008
- Last updated
- 2 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Low-dose naltrexone therapy improves active Crohn's disease. Am J Gastroenterol. 2007 Apr;102(4):820-8. doi: 10.1111/j.1572-0241.2007.01045.x. Epub 2007 Jan 11.
PubMed 17222320Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial. Dig Dis Sci. 2011 Jul;56(7):2088-97. doi: 10.1007/s10620-011-1653-7. Epub 2011 Mar 8.
PubMed 21380937
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Naltrexone in Active Crohn's Disease
- ClinicalTrials.gov ID
- NCT00663117
- Acronym / sponsor ID
- LDN / DK073614 l
- Conditions
- Inflammation, Crohn's Disease
- Keywords
- naltrexone, LDN, IBD, Inflammatory bowel disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Broad Foundation
- Study start
- Sep 2006
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 22 Apr 2008 (estimated)
- Results
- Posted 17 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is hypothesized that the opioid antagonist naltrexone will improve inflammation of the bowel and quality of life in subjects with active Crohn's disease compared to placebo. In order to test this hypothesis the following specific aims are proposed:
- Evaluate the effects of low dose naltrexone compared to placebo on the activity of Crohn's disease by the following end points: Crohn's Disease Activity Index (CDAI), pain assessment, laboratory values (CRP and ESR), endoscopic appearance, histology, and quality of life surveys;
- Examine the effects of naltrexone given over 3 months compared to 6 months for durability of response;
- Determine the safety and toxicity of low dose naltrexone in subjects with active Crohn's disease, and
- Study the mechanism by which naltrexone exerts its effect by measuring plasma enkephalin levels of subjects on therapy.
Purpose statement: The purpose of this study is to evaluate the effects of low dose naltrexone in a blinded placebo controlled study to determine the safety and efficacy of this compound in those with active Crohn's disease.
Detailed description
Study design : The study is designed as a double-blind placebo controlled study for 3 months followed by a pseudo cross-over such that all subjects receiving placebo the first 3 months will receive active drug the second 3 months and all receiving naltrexone the first 3 months remain on the drug the last 3 months of this 6 month study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo, Sugar pill | Placebo comparator | Drug: Naltrexone-HCl, Drug: Placeboplacebo for 3 months blinded then followed by an open-labelled study and all are treated with naltrexone 4.5 mg for 3 additional months |
| Naltrexone-HCl | Active comparator | Drug: Naltrexone-HClSubjects are treated in a blinded fashion for 3 months with naltrexone 4.5 mg po for active Crohn's disease followed an open-labelled study where naltrexone is given an additional 3 months at 4.5 mg po; hence the total treatment interval in this arm is 6 months. The response to the intervention administered is measured in the activity index and mucosal healing by colonoscopy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- All subjects must give written informed consent
- Male or female subjects, > 18 years
- Patients must have endoscopic, histologic, or radiographic confirmed Crohn's Disease.
- Patients must have a Crohn's Disease Activity Index (CDAI) of at least 220 at Baseline
- Stable doses of medications for Crohn's disease over proceeding 4 weeks (for aminosalicylates and steroids: prednisone of 10mg or less daily and Entocort 3 mg/ day are allowed), and 12 weeks for azathioprine or 6-mercaptopurine.)
Key exclusion criteria (9 listed)
- Subjects with ostomies or ileorectal anastomosis from prior surgical colectomy.
- Subjects who received infliximab (Remicade) within 8 weeks of study screening or humira for 4 weeks.
- Subjects requiring steroids either intravenously or prednisone >10mg /day or Entocort > 3 mg daily.
- Subjects with short-bowel syndrome.
- Abnormal liver enzymes at screening visit or known hepatitis or cirrhosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naltrexone-HClAlso: LDN, Revianaltrexone 4.5 mg | Drug | Naltrexone-HCl, Placebo, Sugar pill |
| PlaceboAlso: sugar pillPlacebo | Drug | Placebo, Sugar pill |
Primary outcome
Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;
Time frame: 3 months
The CDAI score is a number which consists of information collected from a 7-day diary from the patient regarding symptoms. It also includes objective information from the physical exam, weight and hemotocrit. Remission is considered a score of 150 or less. Active disease is considered 220 or greater. A response to therapy is considered a decline in the CDAI score of 70-points from baseline.
3 secondary outcomes
Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)
Time frame: Between baseline and 3 months
Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy
Time frame: 12 weeks
Histology Inflammatory Score by Colon Biopsies
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17222320Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Low-dose naltrexone therapy improves active Crohn's disease. Am J Gastroenterol. 2007 Apr;102(4):820-8. doi: 10.1111/j.1572-0241.2007.01045.x. Epub 2007 Jan 11.
- Results publication: PubMed 21380937Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial. Dig Dis Sci. 2011 Jul;56(7):2088-97. doi: 10.1007/s10620-011-1653-7. Epub 2011 Mar 8.
- Penn State Hershey Clinical Trials WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jill P. Smith, M.D. principal investigator
Pennsylvania State University College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naltrexone-HCl in people with Inflammation and Crohn's Disease, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores; (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00663117, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2018.