Naltrexone and Clonidine Combination (ATNC05) in the Treatment of Chronic Back Pain

Study Overview
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Brief Summary
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The study includes back pain of the cervical, thoracic, and the lumbar regions.

Official Title
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A Proof-of-Concept, Randomized, Double-Blind and Placebo Controlled Clinical Trial With Naltrexone and Clonidine Combination (ATNC05) Compared With Placebo in the Treatment of Chronic Back Pain

Conditions
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Back Pain, Lower Back Pain, Cervical Pain

Intervention / Treatment
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* Drug: Naltrexone and Clonidine Combination
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has chronic back pain for > 3 months in the lumbar, thoracic or cervical regions. The average pain intensity scale during the screening week is 4/10 - 8/10 (On an 11-point Numeric Pain Intensity Scale with 0 = no pain and 10 = worst pain imaginable). The subject has not taken Opioid medications 7 days prior to initiation of study drug. The subject has a heart rate of 60bpm or above and/or systolic blood pressure 90 or above. The subject is willing to refrain from using NSAIDS, Acetaminophen or muscle relaxants, unless for rescue, for the duration of the study The subject is willing to refrain from using Opioid medications and excessive alcohol for the duration of the study. The subject is able to read, understand and follow the study instructions, including completion of questionnaires at home. The subject must sign an informed consent document indicating willingness to participate. If the subject is a female, she must be post-menopausal, not currently pregnant or nursing. A female of child bearing potential should be using a reliable contraception method during the course of the study. Exclusion Criteria: The subject has a positive urine drug screen. The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease. The subject has any significant deviations from normal in physical examination, electrocardiogram (ECG), Echocardiogram or clinical laboratory tests, as evaluated by the investigator. The subject has a history of an allergic reaction to the components of the study drug. The subject has acute back or cervical pain. The subject has muscular back or cervical pain. The subject has back or cervical pain other than chronic Radicular pain.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATNC05 - a study drug capsule<br>Naltrexone and Clonidine Combination (ATNC05) | Drug: Naltrexone and Clonidine Combination<br>* subjects will receive 1 study drug capsule by mouth twice daily for 3 weeks, followed by 1 capsule in the morning for 3 days.<br>* Other names: ATNC05;|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* subjects will receive 1 placebo capsule by mouth twice daily for 3 weeks, followed by 1 capsule in the morning for 3 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Brief Pain Inventory 24-hour Pain Scores for average pain (Question #5) | The Brief Pain Inventory is a self-reported medical questionnaire used to measure pain over the past 24-hours - worst pain (Question 3), least pain (Question 4), average pain (Question 5), right now pain (Question 6) and at night pain (Question 7). The score ranges from 0 to 10 (0 - no pain) (10 - intolerable pain). | baseline to week 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Brief Pain Inventory 24-hour assessment of interference in function (Questions 9a - 9i). | BPI Interference; questions 9a - 9i - measures a self-reported assessment of the interference in function because of pain in past 24 hours in general activity, mood, walking ability, normal work, relationship with other people, sleep quality, enjoyment of life, standing ability and sitting ability. Interference scores: 0 (does not interfere) to 10 (completely interferes). | baseline to week 1, week 2 and week 3 | 
| Change From Baseline in Brief Pain Inventory 24-hour subject's Global Impression of Improvement (Question 8) | The Brief Pain Inventory question 8 measures the subject's perception of how much relief he has received at the time of assessment compared with before the start of the study drug. The score is measured in percentage 0% (no relief) to100% (complete relief). | baseline to week 1, week 2 and week 3 | 
| Change From Baseline in the subject's Global Assessment of Treatment Satisfaction today | A self-reported scale that measures Treatment Satisfaction today in (0-10, 0 - none, 10 - most satisfied) | baseline to week 1, week 2 and week 3 | 
| Change from Baseline in the subject's perception of Ability to Tolerate the study drug and the severity of side effects today. | A self-reported scale that measures the ability to tolerate the study drug and the severity of side effects today in (0-10, 0 - No side effects, 10 - intolerable side effects) | baseline to week 1, week 2 and week 3 | 
| Change From Baseline in Oswestry Disability Index and Neck Disability composite scores(ODI), to Week 1, Week 2, and Week 3 | The Oswestry Low Back Pain Disability Questionnaire (Oswestry Disability Index) and Neck Disability composite assesses pain-related disability in persons with low back pain (LBP) and neck pain. The score is recorded in percentage of disability. | baseline to week 1, week 2 and week 3 | 
| Change From Baseline in Roland Morris Disability Questionnaire composite scores(ODI), to Week 1, Week 2, and Week 3 | The Roland Morris Disability Questionnaire consists of 24 statements and the subject is instructed to put a mark next to each appropriate statement. The total score ranges from 0 (no disability) to 24 (severe disability). | baseline to week 1, week 2 and week 3 | 
| Change From Baseline in Vital Signs - systolic blood pressure, diastolic blood pressure, pulse rate and body mass index to Week 1, Week 2, and Week 3. |  | baseline to week 1, week 2 and week 3 | 
| Change from Baseline to week 3 in Laboratory Assessments - Alkaline Phosphatase, Alanine Transaminase - ALT (SGPT), Aspartate transaminase - AST(SGOT), Bilirubin, Total, Serum Creatinine, Blood Urea Nitrogen, Serum Chloride, Potassium, HCO3 |  | baseline to week 1, week 2 and week 3 | 
| Change from Baseline in the investigator's Clinical Global Impression - Severity scale (CGI-S) to Week 1, Week 2, week 3 . | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the investigator to rate the severity of the subject's back pain at the time of assessment, relative to the investigator's past experience. Considering total clinical experience, the subject is assessed on severity of back pain at the time of rating 1, normal; 2, borderline; 3, mild; 4, moderate; 5, marked; 6, severe; or 7, extreme. | baseline to week 1, week 2 and week 3 | 
| Change from Baseline in The investigator's Clinical Global Impression - Improvement scale (CGI-I) to Week 1, Week 2, week 3 | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale, the investigator will rate how much the patient's back pain has improved or worsened relative to a baseline state at the beginning of the study and rate as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. | baseline to week 1, week 2 and week 3 | 
| Change from Baseline in the subject's answer to the question, Are you better off today then the time before starting the study drug?, yes/no, by what percentage? | Answer, yes/no and by 0%-100% (0%-not at all better, 100% - very much better off | baseline to week 1, week 2 and week 3 | 
| Change From Baseline in the subject's answer to the question  Have you been more / less active in the past 24 hrs, comparing to the period before initiating the study drug, please rate in %. | The subjects answer, one of the following choices, - 150%, -100%, -50%, - 25%, 0% - same activity level, +25%, +50%, +100%, +150% | baseline to week 1, week 2 and week 3 | 
| Subject's response to the question, Have you responded to the treatment? | Subject's answer yes/no. | baseline to week 1, week 2 and week 3 | 
| Subject's Global Assessment of Disease Activity Improved / No Change | The Subject answer either Improved or No Change. | baseline to week 1, week 2 and week 3 | 
| Subject's Global Evaluation of Study Medication. | The subject chooses, 1 - Excellent, 2 - Very Good, 3 - Good, 4 - Fair, 5 - Poor | baseline to week 1, week 2 and week 3 | 
| The Subject's Satisfaction with Pain Relief, 0 - 10. | The subject answers on a scale of 0-10, (0 - not satisfied, 10 - very satisfied). | baseline to week 1, week 2 and week 3 | 
| The Subject's Satisfaction with Moving, Standing, Walking and Bending Ability Scale, 0-10. | The subjects answers on a scale of 0-10, (0 - not satisfied, 10 - very satisfied) | baseline to week 1, week 2 and week 3. | 
| Change from Baseline in Brief Pain Inventory 24-hour Pain Scores for worst pain, least pain, right now pain and night pain (Questions 3,4,6 & 7) | The Brief Pain Inventory is a self-reported medical questionnaire used to measure pain over the past 24-hours - worst pain (Question 3), least pain (Question 4), average pain (Question 5), right now pain (Question 6) and at night pain (Question 7). The score ranges from 0 to 10 (0 - no pain) (10 - intolerable pain). | baseline to week 1, week 2 and week 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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back pain, cervical pain, neuropathic pain, radicular pain