The Comparison of Stress Response to Rapid Opioid Detoxification Applying Different Methods of Opioid Antagonism

Study Overview
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Brief Summary
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The aim of this study is to investigate which method of naltrexone induction during rapid opioid detoxification causes stronger stress response and has a higher influence on opioid abstinence caused by opioid induction.

Detailed Description
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Study enrolls opiate addicted patients who are motivated for a long term treatment and full opiate abstinence. Patient is offered to take part in a study. Information is provided regarding protocol, aim and course of study. Patients who are eligible and consent for study commit to follow the pre-study recommendations. Study consists of: Primary assessment - information about study. Assessment of patient according to predefined criteria. Consent form. Allocation of the treatment date. Stabilization - Buprenorphine. Assessment according to SOWS and OWS. Total amount of buprenorphine is recorded. Repeated evaluation - patient after successful stabilization course undergoes urine test for psychotropic substances, blood alcohol level is recorded. If any test is positive patient is not enrolled to study. Correction of opioid withdrawal symptoms - all of the patients receive medicines for opioid detoxification, infusion therapy in predefined doses. Antagonist induction - patients receive opioid antagonist (incremental or standard dose). Withdrawal symptoms are assessed and correction with lorazepam is given if needed. Data collection - data is recorded (demographic, epidemiological, vital signs, opioid withdrawal symptoms, levels of hormones, metabolites, electrolytes).

Official Title
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The Comparison of Stress Response to Rapid Opioid Detoxification Applying Different Methods of Opioid Antagonism With Naltrexone and Sedation

Conditions
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Opiate Addiction

Intervention / Treatment
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* Drug: Naltrexone
* Drug: Clonidine
* Drug: Lorazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Opiate addiction Use of short-acting opiate (morphine or heroine) Age > 18 years Length of opiate addiction > 1 year Patient can make a decision for detoxification and has a capacity to consent for procedure Written consent for procedure Exclusion Criteria: Polyvalent addiction Pregnancy or breast feeding Cardiovascular pathology Acute or chronic kidney disease Decompensated liver pathology (jaundice, ascites, hepatic encephalopathy) Infective complications of opiate addiction (pneumonia, phlegmon, abscess, thombophlebitis, sepsis) Malnutrition (Nutritional risk screening 2002 score ≥3) Diabetes mellitus Previous history of psychosis Glasgow coma scale < 15 Abdominal surgical intervention during last 30 days Cumulative buprenorphine dose for stabilization < 8 mg Positive test for psychoactive substances during treatment Refusal to participate in study at any point of it

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Opioid antagonist induction. Day 4. Duration 12-16 hours. Naltrexone gradual increase from 50 µg p/o to a total dose of 12,5 mg according to a predefined protocol: st hour 50 µg nd hour 50 µg rd hour 100 µg th hour 100 µg th hour 200 µg th hour 400 µg th hour 800 µg th hour 1600 µg th hour 3200 µg th hour 6000 µg Correction of symptoms for opioid abstinence: Clonidine 150 µg p/o every 4 hours (Day 3 and Day 4) Lorazepam 5 mg p/o every 4 hours (Day 3 and Day 4), Lorazepam 2,5 mg po every 4 hours (Day 5, Day 6) | Drug: Naltrexone<br> <br> * Other names: Revia;Drug: Clonidine<br> <br> * Other names: Kapvay;Drug: Lorazepam<br> <br> * Other names: Ativan;|
| Active Comparator: Control<br>Opioid antagonist induction. Day 4. Duration 12-16 hours. Naltrexone single dose 12,5 mg p/o Correction of symptoms for opioid abstinence: Clonidine 150 µg p/o every 4 hours (Day 3 and Day 4) Lorazepam 5 mg p/o every 4 hours (Day 3 and Day 4), Lorazepam 2,5 mg po every 4 hours (Day 5, Day 6) | Drug: Naltrexone<br> <br> * Other names: Revia;Drug: Clonidine<br> <br> * Other names: Kapvay;Drug: Lorazepam<br> <br> * Other names: Ativan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol levels | Cortisol levels were assessed 4 times starting on intervention day (1 hour before intervention, 1, 5 and 23 hours post-intervention) | 2 days | 
| Adrenocorticotropic hormone (ACTH) levels | Cortisol levels were assessed 4 times starting on intervention day (1 hour before intervention, 1, 5 and 23 hours post-intervention) | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stress response levels according to heart rate | Heart rate measurements were taken 4 times a day | 4 days | 
| Stress response levels according to respiratory rate | Respiratory rate measurements were taken 4 times a day | 4 days | 
| Stress response levels according to blood pressure | Blood pressure measurements were taken 4 times a day | 4 days | 
| Changes of potassium concentration due to stress response | Blood samples were taken 3 times a day | 4 days | 
| Changes of sodium concentration due to stress response | Blood samples were taken 3 times a day | 4 days | 
| Changes of chloride concentration due to stress response | Blood samples were taken 3 times a day | 4 days | 
| Changes of magnesium concentration due to stress response | Blood samples were taken 3 times a day | 4 days | 
| Changes of glucose concentration due to stress response | Blood samples were taken 3 times a day | 4 days | 
| Subjective Opiate Withdrawal Scale (SOWS) | Patients were assessed with to SOWS 4 times a day | 4 days | 
| Objective Opiate Withdrawal Scale (OOWS) | Patients were assessed with to OOWS 4 times a day | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid detoxification, Opioid antagonist induction, Conscious sedation