Effects of Intranasal Naloxone on Gambling Urges and Craving in Gambling Disorder (NalGamb)

July 14, 2019 updated by: Hannu Alho, Finnish Institute for Health and Welfare

Double-blind, Placebo-controlled Randomised Study on the Efficacy of Naloxone Nasal Spray for the Treatment of Gambling Disorder

Primary objective:

*To determine whether treatment with naloxone hydrochloride nasal spray reduces gambling urge symptoms in patients with gambling disorder

The secondary objectives of the study are:

  • To determine the effects of naloxone hydrochloride nasal spray on gambling severity, frequency and time, internet use, self-efficacy, quality of life, alcohol consumption, depression
  • To evaluate the safety of naloxone hydrochloride nasal spray in the treatment of gambling disorder

Study Overview

Detailed Description

This is a 12 week, randomised, double-blind, placebo-controlled, parallel group study to determine the efficacy of naloxone hydrochloride nasal spray in gambling disorder. Anticipated number of participants are 126.

Treatment Group A: Naloxone hydrochloride 40mg/ml nasal spray Naloxone hydrochloride will be dosed at 4mg / dose (one spray of 0.1ml of the 40mg/ml formulation into one nostril) up to four times daily as needed in response to gambling urges with at least 2 hours between each dose (within 24 hours from 6am each day) for 12 weeks.

Treatment Group B: Placebo nasal spray One spray of 0.1ml of the placebo formulation in one nostril up to four times daily as needed in response to gambling urges with at least 2 hours between each dose (within 24 hours from 6am each day) for 12 weeks.

Safety parameters:

Study Subjects will be asked to report any changes in health via the daily questionnaire. This will be reviewed weekly and at each study Visit (including phone calls) and any adverse events will be documented in the eCRF. Changes in vital signs and outcome of routine blood analyses will be evaluated.

Adverse events (AEs) will be classified using a coding thesaurus (MedDRA).

Primary endpoint: Gambling symptoms (G-SAS) from Baseline to week 12. Gambling symptoms (G-SAS) from Baseline to week 12.

Study Type

Interventional

Enrollment (Anticipated)

126

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Uusimaa
      • Helsinki, Uusimaa, Finland, 00270
        • National Institute for Health and Welfare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Inclusion criteria:

The Subject must satisfy the following criteria for entry into the study:

  1. Aged 18 to 75 years, fluent in Finnish and able to read and understand the patient information sheet
  2. Provide written, informed consent prior to any study specific procedure being conducted
  3. Gambling problem at pre-screening (SOGS 5 or more points)
  4. Moderate (6-7 criteria met) or severe (8-9 criteria met) GD (DSM-5) assessed by clinical interview with Medical Doctor (MD)
  5. At least 4 weeks since completion of any other previous treatment for GD
  6. At least 8 weeks since completion of any previous treatment with naltrexone or nalmefene
  7. Willingness to comply with all study procedures and visit schedules

Exclusion Criteria:

  • Exclusion criteria:

The Subject will be excluded from the study if any of the following applies:

  1. Two weeks or longer abstinence from gambling prior to randomisation
  2. Known allergic reactions to naloxone or excipients of IMP and placebo
  3. Current use of drugs (opiates, amphetamine, metamphetamine, cocaine, cannabis and benzodiazepines) (as assessed by saliva drug screen, DrugWipe-6)
  4. Subject is taking any prohibited medication (opioid analgesics, any medication delivered to the nose)
  5. Serious mental illness or severe Depression assessed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Disorders (SCID-I, DSM-5) and the Montgomery and Asberg Depression Rating Scale (MADRS) scores 24 points or more
  6. Clinically significant risk of suicide (Columbia-Suicide Severity Rating Scale (C-SSRC))
  7. Women who are pregnant or breastfeeding at screening or Baseline
  8. Serious kidney (P-Creatinine > 110 umol/ml) insufficiency
  9. The Subject/patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
  10. Liver cirrhosis or liver enzyme elevations, ASAT or ALAT >200 (by blood drop test),
  11. Active HCV infection (saliva test, OralQuick-HCV)
  12. The person that met the criteria of vulnerable person according to Finnish Medical Research Act No188/1999 7-10§
  13. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless surgically sterile must use effective contraception (either combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD], intrauterine hormone-releasing system [IUS], vasectomised partner, sexual abstinence (only considered an acceptable method of contraception when it is in line with the subjects' usual and preferred lifestyle), combination of male condom with either cap, diaphragm or sponge with spermicide [double barrier methods]), and willing and able to continue contraception for 1 month after the last administration of IMP. Women using oral contraception must have started using it at least 2 months prior to screening. Women are not considered to be of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms). Or have had a surgical bilateral oophorectomy (with or without hysterectomy) or bilateral tubal ligation at least six weeks before the screening visit. In case of oophorectomy alone, the reproductive status of the woman should have been confirmed by follow up hormone level assessment.
  14. Severe comorbidity (e.g., drug addiction, psychosis, diabetes)
  15. Experimental agents must have been discontinued at least 8 weeks prior to screening for a period equivalent to 5 half-lives of the agent (whichever is longer)
  16. Any diagnosed nasal conditions including abnormal nasal anatomy, nasal symptoms (i.e. blocked nose, nasal polyps etc.), or having product sprayed in to the nasal cavity prior to drug administration
  17. Subject with concurrent disease considered by the investigator to be clinically significant in the context of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: placebo nasal spray
Drug: placebo nasal spray One spray of 0.1ml of the placebo formulation in one nostril up to four times daily as needed in response to gambling urges with at least 2 hours between each dose (within 24 hours from 6am each day) for 12 weeks.
One spray of 0.1ml of the placebo formulation in one nostril up to four times daily as needed in response to gambling urges with at least 2 hours between each dose (within 24 hours from 6am each day) for 12 weeks.
Other Names:
  • Placebo nasal spray with no active ingredients
ACTIVE_COMPARATOR: Naloxone hydrochloride 40mg/ml nasal spray
Naloxone hydrochloride will be dosed at 4mg / dose (one spray of 0.1ml of the 40mg/ml formulation into one nostril) up to four times daily as needed in response to gambling urges with at least 2 hours between each dose (within 24 hours from 6am each day) for 12 weeks.
Naloxone hydrochloride will be dosed at 4mg / dose (one spray of 0.1ml of the 40mg/ml formulation into one nostril) up to four times daily as needed in response to gambling urges with at least 2 hours between each dose (within 24 hours from 6am each day) for 12 weeks.
Other Names:
  • Naloxone 40mg/ml nasal spray when craving to gamble

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Gambling Symptom Assessment Scale (G-SAS) gambling symptom severity and change during the treatment - assessment
Time Frame: Baseline to week, 3, 6, 9 and week 12.
The G-SAS is a 12-item self-rated scale designed to assess gambling symptom severity and change during treatment. The G-SAS is not a diagnostic or screening instrument. Each 12-item scale has a score ranging from 0 - 4 (adjective anchors for 0 and 4 vary for each item). All items ask for an average symptom based on the past 7 days. Items 1 - 4 can be used to assess changes in craving symptoms. Total score ranges from 0 - 48: extreme = 41 - 48, severe = 31 - 40, moderate = 21 - 30, mild = 8 - 20.
Baseline to week, 3, 6, 9 and week 12.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
VAS (gambling craving)
Time Frame: Baseline to Week 3, 6, 9 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 3,6,9,and 12 craving of gambling will be assessed.
Baseline to Week 3, 6, 9 and 12
Gambling severity (PGSI)
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 severity of gambling will be assessed.
Baseline to Week 6 and 12
Gambling severity (DSM-5)
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. From baseline to week 6, and 12 severity of gambling will be assessed.
Baseline to Week 6 and 12
Gambling problems (NODS)
Time Frame: Baseline to Week 3, 6, 9 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 3,6,9,and 12 level of gambling problems will be assessed.
Baseline to Week 3, 6, 9 and 12
Gambling expenditure and frequency
Time Frame: Baseline to Week 12
daily questionnaire / telephone operated (text messages) diary (daily use of sprays, number of doses, gambling expenditure and frequency and possible adverse events) and self-administration of IMP.
Baseline to Week 12
Abstinence of gambling (GASS)
Time Frame: Baseline to Week 3, 6, 9 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 3,6,9,and 12 abstinence of gambling will be assessed.
Baseline to Week 3, 6, 9 and 12
Internet use (Internet disorder scale-9 short form)
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 internet use will be assessed.
Baseline to Week 6 and 12
Quality of life (WHO: EUROHIS-8)
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 quality of life will be assessed.
Baseline to Week 6 and 12
Alcohol consumption (AUDIT)
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 graving of gambling will be assessed.
Baseline to Week 6 and 12
Depression (MADRS)
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 mood will be assessed.
Baseline to Week 6 and 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and proportion of subjects with adverse events
Time Frame: Baseline to week 12 - daily
The use of the daily questionnaire / telephone operated (text messages) diary (daily use of sprays, number of doses, gambling expenditure and frequency and possible adverse events) and self-administration of IMP.
Baseline to week 12 - daily
Assessment of clinical laboratory parameters - Pregnancy test
Time Frame: Screening to Week 6 and 12
The entire study for an individual participant will last 12 weeks. At Screening and week 12 blood pregnancy test and week 6 urine pregnancy test
Screening to Week 6 and 12
Assessment of vital signs - blood pressure, pulse, temperature
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. Assessments at baseline, 6 and 12 vital signs ( blood pressure, pulse and temperature) will be assessed.
Baseline to Week 6 and 12
Assessment of body height
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. Assessments at the baseline, week 6, and week 12. Body height will be assessed.
Baseline to Week 6 and 12
Assessment of body weight
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. Assessment at baseline, 6, and 12 . Body weight will be assessed.
Baseline to Week 6 and 12
Assessment and examination of nasal mucosa
Time Frame: Baseline to Week 6 and 12
The entire study for an individual participant will last 12 weeks. Assessment at baseline, 6, and 12 nasal mucosa will be assessed using Nasal Irritation Scale (0= normal appearing mucosa, no bleeding to 5= Ulcerated lesions, bleeding with requires medical intervention). Assessment is performed by MD.
Baseline to Week 6 and 12
Assessment of smell test
Time Frame: Baseline to Week 12
The entire study for an individual participant will last 12 weeks. Assessments at baseline and week 12 smell will be assessed.Smell test will be conducted at Baseline and Week 12. NIH Toolbox Odour Identification Test: This validated smell identification test uses 'scratch and sniff' technology, and pictures for the multiple-choice options of 9 common smells. It is intended for a rapid research assessment of olfactory ability.
Baseline to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Hannu Alho, Prof., Finnish Institute for Health and Welfare

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 22, 2018

Primary Completion (ANTICIPATED)

August 30, 2019

Study Completion (ANTICIPATED)

March 30, 2020

Study Registration Dates

First Submitted

January 30, 2018

First Submitted That Met QC Criteria

February 5, 2018

First Posted (ACTUAL)

February 12, 2018

Study Record Updates

Last Update Posted (ACTUAL)

July 16, 2019

Last Update Submitted That Met QC Criteria

July 14, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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