Trial Outcomes & Findings for The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease (NCT NCT00715117)

NCT ID: NCT00715117

Last Updated: 2018-09-06

Results Overview

Using adverse events and laboratory values Safety \& toxicity were evaluated between those on placebo for 8 weeks and those on naltrexone for either 8 or 16 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: 8 weeks or 16 weeks
• Results posted on: 2018-09-06

Participant Flow

14 subjects were enrolled in this pilot trial and 2 were screen failures and not randomized or treated

The 2 subjects who were screen failures had PCDAI scores less than 30.

Participant milestones

Measure	A: Placebo Then Naltrexone Subjects will receive placebo for for the first 8weeks then be crossed over to active drug naltrexone for the last 8 weeks	B: Naltrexone Then Naltrexone Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day for 8 weeks followed by the same treatment for an additional 8 weeks
Overall Study STARTED	6	6
Overall Study Completion fo 8 Week Study	6	6
Overall Study COMPLETED	6	5
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	A: Placebo Then Naltrexone Subjects will receive placebo for for the first 8weeks then be crossed over to active drug naltrexone for the last 8 weeks	B: Naltrexone Then Naltrexone Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day for 8 weeks followed by the same treatment for an additional 8 weeks
Overall Study Crohn's flare and rescue with steroids	0	1

Baseline Characteristics

The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease

Baseline characteristics by cohort

Measure	A: Placebo Control Group n=6 Participants Subjects will receive placebo for for the first 8weeks then be crossed over to active drug for the last 8 weeks	B: Naltrexone, Active Drug Group n=6 Participants Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day for 16 weeks	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	12.2 years STANDARD_DEVIATION 3.31 • n=5 Participants	13 years STANDARD_DEVIATION 3.22 • n=7 Participants	12.5 years STANDARD_DEVIATION 3.2 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Pediatric Crohn's Disease Activity Index (PCDAI) score	45 score n=5 Participants	38.3 score n=7 Participants	41.7 score n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks or 16 weeks

Population: The Fisher Exact Test was used to evaluate the number of side effects reported between placebo and naltrexone groups. The Student T-test was used to evaluate the differences between the mena values of laboratory tests.

Using adverse events and laboratory values Safety & toxicity were evaluated between those on placebo for 8 weeks and those on naltrexone for either 8 or 16 weeks.

Outcome measures

Measure	All Participants Pretreament n=6 Participants All participants prior to receiving placebo or naltrexone at week 0	Placebo n=12 Participants Patients were treated with a placebo (sugar pill)for 8 weeks.	Naltrexone Includes all Naltrexone treated participants 8 weeks of treatment.
Number of Patients Reporting Side Effects Sleep disturbance	2 participants	2 participants	—
Number of Patients Reporting Side Effects Unusal Dreams	0 participants	2 participants	—
Number of Patients Reporting Side Effects Twitching	1 participants	1 participants	—
Number of Patients Reporting Side Effects Headaches	1 participants	0 participants	—
Number of Patients Reporting Side Effects Decreased appetite	1 participants	0 participants	—
Number of Patients Reporting Side Effects Nausea	0 participants	1 participants	—
Number of Patients Reporting Side Effects Hair loss	1 participants	0 participants	—
Number of Patients Reporting Side Effects Fatigue	1 participants	0 participants	—
Number of Patients Reporting Side Effects Flushed ears	0 participants	1 participants	—
Number of Patients Reporting Side Effects Papules, rash	1 participants	0 participants	—
Number of Patients Reporting Side Effects Double vision	0 participants	1 participants	—

SECONDARY outcome

Timeframe: Pretreatment and 8 weeks

Population: The power calculations were performed using STPLAN version 4.1. The current investigation was designed as a pseudo-cross over study to increase the number of participants. In the proposed study, it was assumed that 80% would respond to naltrexone and that no more than 25% of the placebo.

Secondary outcome was efficacy on clinical activity. Mean pretreatment PCDAI scores in patients had moderate to severe disease activity at baseline were compared between those who received placebo for 8 weeks and those who received active experimental drug, naltrexone.

The PCDAI score is a number unit that is calculated from symptoms scores by the subject over a 7-day period prior to the visit, laboratory values, height & weight, and physical exam findings. A score of 10 and under denotes "remission". Mild disease (score of 11-30); moderate disease (score of 31-45), a severe disease (scores greater than 45. A decline of 10 points or more is considered "response to therapy". The score can range from 0 to >60 Patient must have a PCDAI score of equal or greater than 30 to qualify for this study (i.e., moderate to severe disease).

Outcome measures

Measure	All Participants Pretreament n=12 Participants All participants prior to receiving placebo or naltrexone at week 0	Placebo n=6 Participants Patients were treated with a placebo (sugar pill)for 8 weeks.	Naltrexone n=12 Participants Includes all Naltrexone treated participants 8 weeks of treatment.
Pediatric Crohn's Disease Activity Index Score (PCDAI)	34.2 units on a scale Standard Error 3.3	30 units on a scale Standard Error 4.9	21.7 units on a scale Standard Error 3.9

SECONDARY outcome

Timeframe: 16 weeks

IMPACT III was a pediatric Crohn's specific quality of life survey used in this study. It examines five major categories influencing the quality of life in children with Crohn's disease including bowel symptoms, systemic symptoms, emotional well-being, social well-being, and body image perception. The IMPACT-III uses 5-point Likert scale ranging from 1 to 5 for all answers. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life. So an increase in score denotes improved Quality of life.

Outcome measures

Measure	All Participants Pretreament n=12 Participants All participants prior to receiving placebo or naltrexone at week 0	Placebo n=12 Participants Patients were treated with a placebo (sugar pill)for 8 weeks.	Naltrexone Includes all Naltrexone treated participants 8 weeks of treatment.
Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy Bowel symptoms	20 units on a scale Standard Error 2.1	23 units on a scale Standard Error 1.9	—
Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy Social well-being	40 units on a scale Standard Error 0.9	45 units on a scale Standard Error 0.8	—
Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy Emotional Well-being	20 units on a scale Standard Error 1.6	24 units on a scale Standard Error 1.5	—
Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy Systemic symtoms	9.8 units on a scale Standard Error 0.2	10.1 units on a scale Standard Error 0.2	—
Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy Body image	10.2 units on a scale Standard Error 0.2	10.3 units on a scale Standard Error 0.2	—

Adverse Events

A: Placebo Control Group

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

B: Naltrexone, Active Drug Group

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	A: Placebo Control Group n=6 participants at risk Subjects will receive placebo for 8weeks	B: Naltrexone, Active Drug Group n=12 participants at risk Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day for 8 or 16 weeks
Psychiatric disorders Sleep disturbance	33.3% 2/6	16.7% 2/12
Psychiatric disorders Unusual dreams	0.00% 0/6	16.7% 2/12
Nervous system disorders Twitching	16.7% 1/6	8.3% 1/12
Nervous system disorders Headaches	16.7% 1/6	0.00% 0/12
Metabolism and nutrition disorders Decreased appetite	16.7% 1/6	0.00% 0/12
Gastrointestinal disorders Nausea	0.00% 0/6	8.3% 1/12
Skin and subcutaneous tissue disorders Hair loss	16.7% 1/6	0.00% 0/12
General disorders Fatigue	16.7% 1/6	0.00% 0/12
Vascular disorders Flushed ears	0.00% 0/6	8.3% 1/12
Skin and subcutaneous tissue disorders Papules, rash	16.7% 1/6	0.00% 0/12
Eye disorders Double vision	0.00% 0/6	8.3% 1/12

Additional Information

Jill P Smith, MD Professor Emeritus of medicine

Pennsylvania State University

Phone: 717-531-3694

Email: jsmith2@psu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee No restrictions by the sponsor. The PI may disclose results after the manuscript has been published.
• Publication restrictions are in place

Restriction type: OTHER