Additional identifiers
EudraCT/CTIS number
2013-002584-25
IRAS number
ClinicalTrials.gov number
Protocol/serial number
17950
Study information
Scientific title
Naltrexone Enhanced Addiction Treatment (NEAT): a randomised controlled trial of the clinical and cost-effectiveness of extended-release naltrexone and oral naltrexone
Acronym
NEAT
Study hypothesis
What is the clinical and cost-effectiveness of enhanced naltrexone (NTX) in the treatment of opioid use disorder? The Naltrexone Enhanced Addiction Therapy for Opioid Use Disorder Trial (NEAT) is the first phase III UK study to coalesce anatagonist medication and behavioural interventions for the treatment of this population.
The study will be implemented in three specialist NHS outpatient addiction clinics in London, Birmingham and Durham (recruitment centres), each with formal links for research trials with a local University.
Three-hundred recently detoxified, formerly dependent heroin users will be randomised to one of three conditions to receive on-site supervised:
1. Thrice-weekly oral active NTX tablets plus placebo extended-release NTX at the start of treatment; or
2. Oral placebo plus active extended-release NTX; or
3. Oral placebo NTX plus placebo extended-release NTX.
Each condition will be delivered over 12 weeks. All participants will receive standard NHS psychological interventions (weekly individual counselling) and a behavioural protocol incentivising clinic attendance to receive trial medication and complete research assessments.
The primary outcome measure is the number of opioid negative urine screening (UDS) tests in treatment (taken thrice weekly during the 12 week treatment phase of the trial; 36 UDS tests in total). In addition to societal focused health-related cost-effectiveness, secondary outcomes include treatment retention/adherence, craving for heroin and cocaine and monitoring of 6-ß-naltrexol (the primary metabolite of NTX). Research worker administered follow-up assessments will be at 16, 24 and 36 weeks after the active 12 week treatment phase.
Ethics approval(s)
London - Dulwich Research Ethics Committee, 06/11/2014, ref: 14/LO/1615
Study design
Non-randomised; Interventional
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Topic: Mental Health; Subtopic: Addictions; Disease: Addictive Substances– illegal drugs
Intervention
1. Active oral Naltrexone, (O-NTX) and matching placebo, nurse administered (thrice-weekly wk 1-4; Monday and Wednesday: 100mg, Friday: 150mg), patient administered dosing (thrice-weekly wk 5-12; Monday and Wednesday: 100mg, Friday: 150mg)
2. Contingency management element, trial nurse administered, increasing value, non-cash (shop voucher) contingency management element to incentivise attendance to complete study measures (thrice-weekly; wk 1-12)
3. Counselling, 12 sessions of practical, manual-guided, personal goal-setting and relapse-prevention oriented counselling with centre clinician (keyworker, weekly, wk 1-12)
4. Single subcutaneous implant, long-acting form of Naltrexone (herein referred to as XR-NTX, naltrexone, 765mg; iGen/Atral-Cipan) and matching placebo (administered on a day-patient basis by a site doctor at beginning of trial week 1)
Intervention type
Mixed
Primary outcome measure
The proportion of opioid negative urines; Timepoint(s): 12 week post randomisation
Secondary outcome measures
1. Adherence; Timepoint(s): end of trial
2. Self-reported heroin use via Time-Line Follow-Back (TLFB) interview; Timepoint(s): 16, 24 and 36 weeks
3. Treatment retention; Timepoint(s): end of trial
Overall study start date
01/06/2015
Overall study end date
31/05/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Inclusion criteria for the study are intended to be as close to clinical practice as possible. Each participant in the trial must meet all of the following criteria:
1. Is 18 years of age or older
2. Has been given 48 hours to consider and demonstrate verbal understanding of the study patient information material, is able to provide written consent, and can understand and confirm willingness to comply with the protocol.
3. Has a diagnosis of opioid use disorder (heroin; DSM-5: past 12 months), based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, using the MINI Neuropsychiatric Interview (version 6) conducted at baseline.
4. Is completing or has recently completed an inpatient or outpatient treatment for opioid detoxification, or has been completely and continuously abstinent from all opioids for at least seven days.
5. Has no tolerance to opioids, as verified by a negative urine toxicology screening test prior to randomisation (using a Morphine 2000 [opioid class] instant result immunoassay device).
6. Passes a naloxone challenge test (to confirm zero opioid tolerance by demonstrating no clinical sign or subjective report of opioid withdrawal before randomisation and prior to implant procedure) NB: Individuals failing screening will be allowed to enter screening once more (only) after one month.
7. Is voluntarily seeking opioid antagonist treatment for opioid use disorder.
8. Lives in stable/secure accommodation in the community.
9. Has a personal (mobile/cellular) phone, and is able to nominate at least one locator individual (e.g. a family member, friend or recovery mentor) with a verifiable address and a telephone number to assist with the arrangement of follow-up appointments as required.
10. If female, is not pregnant or breast feeding and agrees to use a birth control method (either oral hormonal contraceptives, barrier [condom or diaphragm], or Nexplanon implant) for the duration of the study
Participant type(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
Planned Sample Size: 300; UK Sample Size: 300
Participant exclusion criteria
Otherwise eligible individuals who meet any of the following criteria will be excluded from the study:
1. Clinically significant medical condition or observed abnormalities on physical examination or laboratory investigation, including but not limited to: Uncontrolled hypertension; Significant heart disease (including angina and myocardial infarction in past 12 months)
Any ECG/cardiovascular abnormality which, in the investigator’s judgment, is clinically significant
2. Severe alcohol dependence and/or alcohol intoxication (breathalysed alcohol level <0.35); or alcohol withdrawal
3. Positive naloxone challenge test at randomization (confirming opioid use).
4. Active hepatitis or aspartate aminotransferase, alanine aminotransferase (>3x the upper limit of the normal range)
5. Currently taking oral or depot naltrexone therapy or enrolment in any form of naltrexone therapy within 90 days prior to study screening
6. Current criminal justice involvement with legal proceedings (not including current probationary supervision) and, in the opinion of the clinical worker is expected to fail to complete the study protocol due to re-incarceration or relocation from the centre’s catchment area
7. Current (past 30 day) suicidal ideation/plan, or recent (past six months) suicidal ideation or suicide attempt
8. Active, uncontrolled severe mental illness (e.g. psychosis, bipolar I disorder, schizoaffective disorder) and/or a history or evidence of organic brain disease or dementia that would compromise the participant’s ability to comply with the study protocol
Recruitment start date
01/06/2015
Recruitment end date
31/05/2016
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
King's College London
Institute of Psychiatry
London
SE5 8AF
United Kingdom
Sponsor information
Organisation
King's College London
Sponsor details
Room 1.8
Hodgkin Building
Guy's Campus
London
SE1 4UL
England
United Kingdom
Sponsor type
Hospital/treatment centre
Website
ROR
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/01/2019 | 01/02/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |