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

Primary Purpose

Pathological Gambling, Gambling Disorder, Opioid Antagonist

Status
Unknown status
Phase
Phase 2
Locations
Finland
Study Type
Interventional
Intervention
Naloxone hydrochloride
Placebo
Sponsored by
Finnish Institute for Health and Welfare
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pathological Gambling

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • National Institute for Health and Welfare

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

placebo nasal spray

Naloxone hydrochloride 40mg/ml nasal spray

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

The Gambling Symptom Assessment Scale (G-SAS) gambling symptom severity and change during the treatment - assessment
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.

Secondary Outcome Measures

VAS (gambling craving)
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.
Gambling severity (PGSI)
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 severity of gambling will be assessed.
Gambling severity (DSM-5)
The entire study for an individual participant will last 12 weeks. From baseline to week 6, and 12 severity of gambling will be assessed.
Gambling problems (NODS)
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.
Gambling expenditure and frequency
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.
Abstinence of gambling (GASS)
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.
Internet use (Internet disorder scale-9 short form)
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 internet use will be assessed.
Quality of life (WHO: EUROHIS-8)
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 quality of life will be assessed.
Alcohol consumption (AUDIT)
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 graving of gambling will be assessed.
Depression (MADRS)
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 mood will be assessed.

Full Information

First Posted
January 30, 2018
Last Updated
July 14, 2019
Sponsor
Finnish Institute for Health and Welfare
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1. Study Identification

Unique Protocol Identification Number
NCT03430180
Brief Title
Effects of Intranasal Naloxone on Gambling Urges and Craving in Gambling Disorder
Acronym
NalGamb
Official Title
Double-blind, Placebo-controlled Randomised Study on the Efficacy of Naloxone Nasal Spray for the Treatment of Gambling Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 22, 2018 (Actual)
Primary Completion Date
August 30, 2019 (Anticipated)
Study Completion Date
March 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Finnish Institute for Health and Welfare

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pathological Gambling, Gambling Disorder, Opioid Antagonist, Naloxone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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. One spray of naloxone hydrochloride 40mg/ml nasal spray contains 4 mg naloxone hydrochloride in a formulation of benzalkonium chloride, sodium edetate, sodium chloride, hydrochloric acid and purified water. 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. One spray of placebo nasal spray contains benzalkonium chloride, sodium edetate, sodium chloride, hydrochloric acid and purified water
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Double Blind
Allocation
Randomized
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
placebo nasal spray
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Naloxone hydrochloride 40mg/ml nasal spray
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Naloxone hydrochloride
Other Intervention Name(s)
Naloxone 40mg/ml nasal spray when craving to gamble
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo nasal spray with no active ingredients
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Gambling Symptom Assessment Scale (G-SAS) gambling symptom severity and change during the treatment - assessment
Description
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.
Time Frame
Baseline to week, 3, 6, 9 and week 12.
Secondary Outcome Measure Information:
Title
VAS (gambling craving)
Description
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.
Time Frame
Baseline to Week 3, 6, 9 and 12
Title
Gambling severity (PGSI)
Description
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 severity of gambling will be assessed.
Time Frame
Baseline to Week 6 and 12
Title
Gambling severity (DSM-5)
Description
The entire study for an individual participant will last 12 weeks. From baseline to week 6, and 12 severity of gambling will be assessed.
Time Frame
Baseline to Week 6 and 12
Title
Gambling problems (NODS)
Description
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.
Time Frame
Baseline to Week 3, 6, 9 and 12
Title
Gambling expenditure and frequency
Description
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.
Time Frame
Baseline to Week 12
Title
Abstinence of gambling (GASS)
Description
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.
Time Frame
Baseline to Week 3, 6, 9 and 12
Title
Internet use (Internet disorder scale-9 short form)
Description
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 internet use will be assessed.
Time Frame
Baseline to Week 6 and 12
Title
Quality of life (WHO: EUROHIS-8)
Description
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 quality of life will be assessed.
Time Frame
Baseline to Week 6 and 12
Title
Alcohol consumption (AUDIT)
Description
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 graving of gambling will be assessed.
Time Frame
Baseline to Week 6 and 12
Title
Depression (MADRS)
Description
The entire study for an individual participant will last 12 weeks. From baseline to weeks 6, and 12 mood will be assessed.
Time Frame
Baseline to Week 6 and 12
Other Pre-specified Outcome Measures:
Title
Number and proportion of subjects with adverse events
Description
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.
Time Frame
Baseline to week 12 - daily
Title
Assessment of clinical laboratory parameters - Pregnancy test
Description
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
Time Frame
Screening to Week 6 and 12
Title
Assessment of vital signs - blood pressure, pulse, temperature
Description
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.
Time Frame
Baseline to Week 6 and 12
Title
Assessment of body height
Description
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.
Time Frame
Baseline to Week 6 and 12
Title
Assessment of body weight
Description
The entire study for an individual participant will last 12 weeks. Assessment at baseline, 6, and 12 . Body weight will be assessed.
Time Frame
Baseline to Week 6 and 12
Title
Assessment and examination of nasal mucosa
Description
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.
Time Frame
Baseline to Week 6 and 12
Title
Assessment of smell test
Description
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.
Time Frame
Baseline to Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Inclusion criteria: The Subject must satisfy the following criteria for entry into the study: Aged 18 to 75 years, fluent in Finnish and able to read and understand the patient information sheet Provide written, informed consent prior to any study specific procedure being conducted Gambling problem at pre-screening (SOGS 5 or more points) Moderate (6-7 criteria met) or severe (8-9 criteria met) GD (DSM-5) assessed by clinical interview with Medical Doctor (MD) At least 4 weeks since completion of any other previous treatment for GD At least 8 weeks since completion of any previous treatment with naltrexone or nalmefene 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: Two weeks or longer abstinence from gambling prior to randomisation Known allergic reactions to naloxone or excipients of IMP and placebo Current use of drugs (opiates, amphetamine, metamphetamine, cocaine, cannabis and benzodiazepines) (as assessed by saliva drug screen, DrugWipe-6) Subject is taking any prohibited medication (opioid analgesics, any medication delivered to the nose) 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 Clinically significant risk of suicide (Columbia-Suicide Severity Rating Scale (C-SSRC)) Women who are pregnant or breastfeeding at screening or Baseline Serious kidney (P-Creatinine > 110 umol/ml) insufficiency The Subject/patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason. Liver cirrhosis or liver enzyme elevations, ASAT or ALAT >200 (by blood drop test), Active HCV infection (saliva test, OralQuick-HCV) The person that met the criteria of vulnerable person according to Finnish Medical Research Act No188/1999 7-10§ 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. Severe comorbidity (e.g., drug addiction, psychosis, diabetes) 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) 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 Subject with concurrent disease considered by the investigator to be clinically significant in the context of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hannu Alho, Prof.
Organizational Affiliation
Finnish Institute for Health and Welfare
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institute for Health and Welfare
City
Helsinki
State/Province
Uusimaa
ZIP/Postal Code
00270
Country
Finland

12. IPD Sharing Statement

Plan to Share IPD
No

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Effects of Intranasal Naloxone on Gambling Urges and Craving in Gambling Disorder

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