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

NCT ID: NCT03430180

Last Updated: 2019-07-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-22
• Study Completion Date: 2020-03-30

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.

Conditions

Pathological Gambling; Gambling Disorder; Opioid Antagonist; Naloxone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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 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.

Group Type: ACTIVE_COMPARATOR

Naloxone hydrochloride

Intervention Type: DRUG

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.

Interventions

Naloxone hydrochloride

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

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Naloxone 40mg/ml nasal spray when craving to gamble; Placebo nasal spray with no active ingredients

Eligibility 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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Finnish Institute for Health and Welfare

OTHER_GOV

Sponsor Role: lead

Responsible Party

Hannu Alho

Research professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hannu Alho, Prof.

Role: PRINCIPAL_INVESTIGATOR

Finnish Institute for Health and Welfare

Locations

National Institute for Health and Welfare

Helsinki, Uusimaa, Finland

Countries

Finland

Other Identifiers

2017-001946-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NalGamb

Identifier Type: -

Identifier Source: org_study_id