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

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

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.

Study Overview

• Status: Completed
• Conditions: Opiate Addiction
• Intervention / Treatment: Drug: Clonidine; Drug: Naltrexone; Drug: Lorazepam

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Lithuania
  • Vilnius, Lithuania, LT-04130
    • Republic Vilnius University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 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: Clonidine; Other Names: Catapres; Kapvay; Drug: Naltrexone; Other Names: Revia; Vivitrol; Drug: Lorazepam; Other Names: Ativan
Active Comparator: Control; 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: Clonidine; Other Names: Catapres; Kapvay; Drug: Naltrexone; Other Names: Revia; Vivitrol; Drug: Lorazepam; Other Names: Ativan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vilnius University
• Investigators: Principal Investigator: ROBERTAS BADARAS, MD, Vilnius University Clinic of Anaesthesiology and Intensive Care; Study Director: JUOZAS IVASKEVICIUS, PROFESSOR, Vilnius University Clinic of Anaesthesiology and Intensive Care

Publications and helpful links

Helpful Links

• Intermediate data

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: January 18, 2015
• First Submitted That Met QC Criteria: February 11, 2015
• First Posted (Estimate): February 12, 2015

Study Record Updates

• Last Update Posted (Estimate): February 12, 2015
• Last Update Submitted That Met QC Criteria: February 11, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Conscious sedation; Opioid detoxification; Opioid antagonist induction
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Antiemetics; Gastrointestinal Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Narcotic Antagonists; Anticonvulsants; Alcohol Deterrents; Sympatholytics; Naltrexone; Clonidine; Lorazepam
• Other Study ID Numbers: 158200-01-443-124