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Trial registered on ANZCTR


Registration number
ACTRN12613000539730
Ethics application status
Approved
Date submitted
11/05/2013
Date registered
14/05/2013
Date last updated
5/11/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of Instruments and Procedures Used to Measure Opioid Withdrawal in Opioid Dependent Participants Who are Seeking to Discontinue Methadone Opioid Substitution Treatment (OST)
Scientific title
Evaluation of Instruments and Procedures Used to Measure Opioid Withdrawal in Opioid Dependent Participants Who are Seeking to Discontinue Methadone Opioid Substitution Treatment (OST)
Secondary ID [1] 282095 0
Nil known
Universal Trial Number (UTN)
U1111-1140-3060
Trial acronym
Opioid Withdrawal Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid Dependency 288595 0
Condition category
Condition code
Mental Health 288926 288926 0 0
Addiction

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
To be eligible, participants must opioid dependent and enrolled in a methadone maintenance programme but seeking to withdraw from methadone. They must be on stable doses of methadone for at least 30 days prior to Screening.

Participants who meet eligibility criteria will undergo a medically supervised OST withdrawal. Their methadone will be replaced with CR morphine twice daily while they are out-patients (Day -7 to Day -3). An equivalent dose to the methadone will be administered as CR morphine an (using a 1:4 ratio). The participant’s response to CR morphine dosing will be monitored for at least 4 hours post dosing and the investigator may adjust the dose to 1:3 to 1:5 ratios depending on participant response.

Participants will be admitted to the Clinical Site on Day -2 and their CR morphine will be replaced with immediate release morphine administered orally as 10mg four times a day on Day -2 and Day -1. On Day 1 the morphine will be with-held; Medical treatment will be provided to minimize symptoms during the withdrawal period.

The following rating scales will be used in this study:
(1)These will be collected to assess psychological and neurological safety and drug effects.
- The Columbia Suicide Severity Rating Scale (C-SSRS): from screening (between Day -28 and Day -9) until Day 3,
- Psychotomimetic Rating Scale (PRS): from screening (between Day -28 and Day -9) until Day 1,
- Mood Visual Analog Scale (Mood VAS): from screening (between Day -28 and Day -9) until the follow-up Visit one week after discharge from the Clinical Site at Day 3,
- Addiction Research Center Inventory (ARCI), from screening (between day -28 and Day -9) until Day 3,
- Addiction Severity Index (ASI):from screening (between Day -28 and Day -9) until Day -2,
- Readiness for Change (RtC):from screening (between Day -28 and Day -9) until Day -2,

(2) Opiate Withdrawal scales will be used to evaluate the progression and suppression of Opiate withdrawal compared to the participant’s baseline:
- Handelsman-Kanof OOWS/SOWS and COWS instruments will be used to assess opioid withdrawal. These are conducted from inital screening until the follow-up Visit 1 (one week after their discharge from the Clinical Site at Day 3).

The resumption of methadone OST may occur when the participant’s withdrawal symptoms have not been controlled with medical intervention and the intensity is to the point where the participant requests OST. Methadone OST may also be initiated at the investigator’s discretion when his clinical evaluation indicates the participant’s withdrawal is increasing and not responding to medical intervention.

All doses of morphine will be administered at the Clinical Site and mouth checks will be performed to ensure compliance.
Intervention code [1] 286700 0
Not applicable
Comparator / control treatment
No comparator or control is involved in this study. It is an open-label observation study of the effects of withdrawing opioid substitution treatment. Even though CR and IR morphine is administered during the study, their administration is to allow observation the effects of opioid withdrawal (the purpose of the study is not to observe the effects of the morphine)
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289052 0
The objective of this study isto evaluate the instruments and procedures to be used in a subsequent study of the safety and tolerability of noribogaine in opioid dependent Participants.

Primary Endpoint: Evaluate the usefulness of SOWS/OOWS and COWS to define withdrawal
Timepoint [1] 289052 0
SOWS/OOWS and COWS Assessments will be done at the initial screening between Day -28 to Day -9, Day -8 pre methadone dose and 2 and 4 hours post dosing, Day-7 at pre CR morphine dose, 2, 4 and 12 hours post dosing, Day -6 to Day -3 prior to the 8AM CR morphine dosing, Day -2 and -1 prior to morphine dosing at 8AM and 5PM, Day 1 baseline and at 1, 2, 4, 6, 8 and 12, 24, 28, 32, 36 and 48 hours after holding the 8AM morphine dose and at Visit 1 (one week after discharge from the Clinical Site at Day 3).
Secondary outcome [1] 301644 0
Secondary Endpoint: Evaluate the usefulness of the following scales:
Addiction Severity Index (ASI)
Addiction Research Center Inventory (ARCI)
Drug History Questionnaire (DHQ)
Hospital Anxiety and Depression Scale (HADS)
Mini International Neuropsychiatric Interview (MINI)
Psychotomimetic Rating Scale (PRS)
Mood Visualization Analog Scale (Mood VAS)
Readiness to Change (RtC)

The data from these scales will be summarised using descriptive statistics (mean, median, standard deviation, inter-quartile range and range) for the quantitative variables. Categorical variables will be summarized by counts and percentages. The scales will only be useful for subsequent research if they reflect the effects of opioid withdrawal in the study population.
Timepoint [1] 301644 0
The timepoints for the secondary endpoints vary for each scale; the timepoints for each scale are listed below:

The PRS will be assessed at the initial screening (between Days -28 to Day -9); pre CR morphine does on Day -7 and Day 1 baseline and 3.5 hours post dosing.

ARCI will be assessed at the initial screening (between Day -28 to Day -9), Day 1 at approximately 12 noon, and Day 3 prior to discharge.

The participant will complete the ASI at the initial screening and Day -2.

CSSRS will be assessed at the initial screening (between Day -28 to Day -9) and Day 3.

The participant will be asked to complete the 5 Mood VAS assessments at initial Screening (Day -28 to Day -9); Day -8 pre methadone dose and 1, 2, 3 and 4 hours post dosing, Days -7 at pre CR morphine dosing and 2, 4 and 12 hours post dosing, Day -6 to Day -3 prior to the 8AM CR morphine dose, Days -2 and -1 prior to morphine dosing at 8AM and 5PM, on Day 1 at baseline and at 1, 2, 3, 4, 5, 6, 8, 10 12, 24, 28, 32, 36 and 48 hours after holding the 8AM morphine dose and at follow up Visit 1 (one week after Discharge from the Clinical Site at Day 3).

The participant will be asked to complete the RtC at the initial screening and Day -2.

The MINI will be used to assess psychological health and drug and alcohol use. The MINI will be conducted at inital Screening (between Day -28 and Day -9)

Eligibility
Key inclusion criteria
The main inclusion criteria are opioid dependent male and female adults (18-55 years) who provide written consent and are on stable doses of methadone through the OST programme. Participants cannot have any other major illnesses or disorders and must be willing to comply with the restrictions of the study.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include current treatment for hepatitis C; HIV positive; DSM IV Axis I diagnosis of psychotic disorders; specified excluded concomitant medications; DSM IV criteria for dependence on substances other than opioids, caffeine, and/or nicotine.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is a small study of approximately 6 participants. Therefore descriptive statistics (mean, median, standard deviation, inter-quartile range and range) will be used to summarize the quantitative variables and categorical variables will be summarized by counts and percentages.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4903 0
New Zealand
State/province [1] 4903 0
Otago

Funding & Sponsors
Funding source category [1] 286869 0
Commercial sector/Industry
Name [1] 286869 0
DemeRx Inc
Address [1] 286869 0
4400 Biscayne Blvd., Suite 580

Miami, FL 33137 USA

Country [1] 286869 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
DemeRx Inc
Address
4400 Biscayne Blvd., Suite 580

Miami, FL 33137 USA

Country
United States of America
Secondary sponsor category [1] 285660 0
None
Name [1] 285660 0
Address [1] 285660 0
Country [1] 285660 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288931 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 288931 0
Health and Disability Ethics Committees
1 The Terrace
PO Box 5013
Wellington
6011
Ethics committee country [1] 288931 0
New Zealand
Date submitted for ethics approval [1] 288931 0
07/03/2013
Approval date [1] 288931 0
09/04/2013
Ethics approval number [1] 288931 0
13/STH/24

Summary
Brief summary
The objective of this study is to evaluate the instruments and procedures to be used in a subsequent study of the
safety and tolerability of noribogaine in opioid dependent Participants. In particular, this study will evaluate the
ability of various assessment scales to detect the signs and symptoms of opioid withdrawal in the study
population.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38386 0
Prof Paul Glue
Address 38386 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 913
Dunedin 9016
New Zealand
Country 38386 0
New Zealand
Phone 38386 0
+64 21 243 3372
Fax 38386 0
Email 38386 0
paul.glue@otago.ac.nz
Contact person for public queries
Name 38387 0
Ms Linda Folland
Address 38387 0
Zenith Technology Ltd
156 Frederick Street
(P O Box 1777)
Dunedin 9016
Country 38387 0
New Zealand
Phone 38387 0
+64 3 477 9669
Fax 38387 0
Email 38387 0
Linda.Folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 38388 0
Dr Lawrence T. Friedhoff
Address 38388 0
DemeRx, Inc, 4400 Biscayne Blvd., Suite 580

Miami, FL 33137 USA
Country 38388 0
United States of America
Phone 38388 0
+1 201 425 1913
Fax 38388 0
+1 305 405 1701
Email 38388 0
Friedhoffl@demerx.us

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary