Condition category
Mental and Behavioural Disorders
Date applied
08/01/2015
Date assigned
12/01/2015
Last edited
12/01/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Plain English summary under review

Trial website

Contact information

Type

Scientific

Primary contact

Dr Peter Morgan

ORCID ID

Contact details

King's College London
Institute of Psychiatry
P043
16 De Crespigny Park
London
SE5 8AF
United Kingdom

Additional identifiers

EudraCT number

2013-002584-25

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

14/LO/1615

Study design

Non-randomised; Interventional

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below 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

Phase

Drug names

Primary outcome measures

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 trial start date

01/06/2015

Overall trial end date

31/05/2016

Reason abandoned

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

Patient

Age group

Adult

Gender

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

United Kingdom

Trial 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
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes