Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04167306
Other study ID # COMB-BO8
Secondary ID 2018-000048-24
Status Completed
Phase Phase 2
First received
Last updated
Start date March 4, 2019
Est. completion date December 15, 2022

Study information

Verified date December 2023
Source Vastra Gotaland Region
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The COMB study is a randomized double-blind placebo-controlled multicenter trial in Sweden on the efficacy of varenicline and bupropion, in combination and alone, for treatment of alcohol use disorder (AUD). Study design overview: A 13-weeks (91 days) multicenter clinical trial with four parallel groups. 95 subjects per treatment arm will be randomized into the study. 380 subjects with AUD will be randomized in total.


Description:

Varenicline (Champix®) and bupropion (Zyban®, patent time expired) are approved and marketed in Europe and US for smoking cessation in nicotine use disorder, and for treatment of major depression (bupropion). There is clinical evidence of an additive effect of the drug combination of varenicline and bupropion on smoking cessation. Varenicline has been shown in two RCTs to reduce also alcohol intake in subjects with AUD. It is hypothesized that bupropion will enhance the effect of varenicline and that the combined effect size will be greater than that of approved therapies for AUD. As efficacy endpoint, the trial uses the alcohol specific biomarker for alcohol intake, phosphatidylethanol in blood (B-PEth). Outcome will also be measured by self-reported alcohol consumption, the standard effect measure in AUD trials.This will be the first trial using the biomarker B-PEth as primary outcome variable. The use of a specific objective marker is expected to increase chances for detecting treatment effects. Development phase: II Number of randomized subjects: 380 subjects with AUD. 95 subjects per treatment arm will be randomized into the study. Number of sites: Approximately 5 study sites in Sweden Investigational medicinal products, dosages and administration: There will be two separate study kits for IMP 1 and IMP 2 Investigational medicinal product 1 (IMP1): Varenicline 1 mg x 2 p.o. daily. The pharmaceutical formulation will be encapsulated tablets for oral use. Varenicline will be escalated from 0.5 to 2 mg daily during the first week. Investigational medicinal product 2 (IMP 2): Bupropion SR 150 mg x 2 p.o. daily. The pharmaceutical formulation will be encapsulated sustained release (SR) tablets for oral use. Bupropion will be escalated from 150 to 300 mg daily during the first week. IMP 1 and IMP 2 are distributed at 7 occasions: Day 0, Day 7, Day 21, Day 35, Day 49, Day 63 and Day 77. The doses and route of administration for varenicline and bupropion are those approved and recommended as oral formulations for smoking cessation. The trial comprises 9 study visits over 91 days: Screening visit,Day 0, Day 7, Day 21, Day 35, Day 49, Day 63, Day 77 and Day 91. Randomization is carried out according to block randomization and eligible subjects are randomized to one of the below described intervention arms. The study will be performed in accordance with the study protocol, with the latest version of the Declaration of Helsinki, in accordance with GCP principles (ICH-GCP E6-R2), and applicable regulatory requirements in Sweden . The study is approved by competent authority (the Swedish Medical Product Agency) and the Etics committee. The trial is monitored by an independent monitor according to GCP principles.


Recruitment information / eligibility

Status Completed
Enrollment 388
Est. completion date December 15, 2022
Est. primary completion date December 15, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 25 Years to 70 Years
Eligibility Inclusion Criteria: 1. Signed informed consent 2. Blood alcohol level below <0.1‰ (0.1 g/L) at signing informed consent 3. 25-70 years of age at screening 4. Moderate and severe AUD according to DSM-V (meeting =4 out of 11 criteria) 5. B-PEth levels of =0.5 µmol/L at screening visit (visit 1) 6. Continuous high alcohol consumption over the last 3 months prior to screening as defined by at least 2 HDD per week on a typical week 7. Available phone number for contact 8. Ability to speak and write in Swedish Exclusion Criteria: 1. Total abstinence between screening and randomization visit 2. Treatment of alcohol withdrawal within 30 days of study initiation 3. Pharmacological treatment within 3 months of study initiation and during the study period that may affect alcohol consumption, including but not exclusive to, varenicline, bupropion, disulfiram, acamprosate, naltrexone, nalmefene, baclofen, topiramate, ondansetron, mirtazapine, methylphenidate, dexamphetamine, atomoxetine, pregabalin, buprenorphine and methadone 4. Non-pharmacological treatment within 3 months of study initiation and during the study period that may affect alcohol consumption 5. Current continuous use of antidepressants, opioid analgesics, benzodiazepines, zopiclone, zolpidem, hydroxyzine, alimemazine, propiomazine, or other sedatives. (The sporadic use of these compounds is accepted.) 6. Any concurrent medication that may affect the results of the trial or is considered to compromise the safety of the participants in the trial. (See SmPCs for possible interactions.) 7. Laboratory hepatic values of >3 times the upper limit of the normal range, creatinine clearance <30 ml/min, or other clinically significant abnormalities in the screening laboratory values 8. Blood pressure =180/110 at screening 9. Pregnancy, breast-feeding and for premenopausal women, not using one of the contraceptive methods oral contraceptive, intrauterine contraceptive device (copper or hormonal) or subcutaneous inplant. 10. Diabetes mellitus type 1 and diabetes mellitus type 2 in need of insulin treatment 11. Any current psychiatric or somatic disorder or condition that may affect assessments or compromise participant's safety during the trial 12. ASRS- v1.1, part A score =4 in the marked cut-off section 13. MADRS score = 20 14. Current depression that is not mild (mild depression is accepted) 15. Suicidality 16. Current illicit drug use based on urine-toxicity test and DUDIT 17. History of delirium tremens or abstinence-induced seizures within 5 years of study initiation 18. Epilepsy or seizures other than alcohol-induced, lifetime 19. Severe sleep disturbances 20. Need of alcohol detoxification 21. Living conditions not appropriate to fulfil study requirements 22. Use of herbal drugs/tea and supplementations possibly affecting outcome or safety 23. Previous randomization in this trial or participation in another trial within 3 months of enrollment into this trial. 24. Additional factors that render the participant unable to complete the study, as judged by the investigator

Study Design


Intervention

Drug:
Varenicline Tartrate 1 mg b.i.d
Capsules for oral use
Bupropion Hydrochloride 150 mg b.i.d
Capsules for oral use
Other:
Placebo for varenicline
Capsules for oral use
Placebo for bupropion
Capsules for oral use

Locations

Country Name City State
Sweden Beroendekliniken, Sahlgrenska University Hospital, Västra Götalandsregionen Gothenburg
Sweden Linköping University Hospital Linköping Region Östergötland
Sweden Beroendecentrum Malmö Malmö Region Skåne
Sweden Stockholm Centre for Dependency Disorders, Stockholm Stockholms Läns Sjukvårdområde

Sponsors (1)

Lead Sponsor Collaborator
Vastra Gotaland Region

Country where clinical trial is conducted

Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Primary Alcohol Consumption as Measured by Phosphatidylethanol (PEth) in Blood B-PEth: Objective marker for alcohol consumption measured in blood, measured at every study visit. Analysed as mean reduction of PEth per treatment arm, mITT. PEth is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)
Primary Alcohol Consumption as Measured by Heavy Drinking Days (HDD) HDD is obtained by the time Line Follow Back procedure, defined as =70 grams for men and =56 grams for women according to FDA's guidelines. Analysed as mean reduction in HDD share per treatment arm, for mITT Number of HDD by 14 days is defined as a mean over the 8-week steady state active treatment period (Day 21-Day77) . ( D21-D77)/4 in order to get a 14 day-period measurment.
Secondary CDT The indirect alcohol marker carbohydrate deficient transferrin CDT is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)
Secondary GGT The indirect alcohol marker gamma glutamyl transferase GGT calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)
Secondary Self-reported Alcohol Consumption Measured by Time-lime-follow-back Mean grams of alcohol per day
Number of drinking days
Number of drinks per drinking days
Number of abstaining days
CDT is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)
Secondary Alcohol Use Identification Test Total score of Alcohol Use Identification Test Mean difference between total score obtained at baseline and visit 1
Secondary Self-reported Alcohol Craving Alcohol craving as measured by a Visual Analogue Scale (VAS) Scale range: 0-100 mm. Minimum value: 0 = No craving. Maxumum value: 100 Maximum= Very strong craving. Craving is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)
Secondary Nicotine Use Nicotine use measured by the nicotine saliva marker cotinine in saliva 77 day-interval. Mean difference between cotinine concentration assessed at Day o and Day 77
Secondary The Temporal Experience of Pleasure Scale (TEPS) A 17-item scale with anticipatory and consummatory components of the experience of pleasure. The scale is used as a proxy to assess a hypodopaminergic state. Worse Outcome: A lower score indicates low experience of pleasure (=proxy for hypodopaminergic state). Better outcome:A high score indicates high experience of pleasure. 77 day-interval. Mean difference between total scale score assessed at Day 0 and Day 77
Secondary The Continous Performance Test + Activity Test A neuropsychiatric tool addressing inattention, impulsivity and activity 77 day-interval. Mean difference between outcome measure assessed at Day o and Day 7.
Secondary Plasma Concentration of Varenicline (ng/ml) Mean concentration of values obtained at visit 4 and visit 6 14 day-interval. Obtained twice, at Day 21 and Day 49 during IMP steady state. Correlation between plasma concentration of varenicline and above described outcome measures
Secondary Plasma Concentration of Bupropion (ng/ml) Mean concentration of values obtained at visit 4 and visit 6 14 day-interval. Obtained twice, at Day 21 and Day 49 during IMP steady state. Correlation between plasma concentration of bupropion and above described outcome measures
See also
  Status Clinical Trial Phase
Recruiting NCT04788004 - Long-term Recovery: Longitudinal Study of Neuro-behavioral Markers of Recovery and Precipitants of Relapse
Recruiting NCT05684094 - Mechanisms of Risky Alcohol Use in Young Adults: Linking Sleep to Reward- and Stress-Related Brain Function N/A
Completed NCT03406039 - Testing the Efficacy of an Online Integrated Treatment for Comorbid Alcohol Misuse and Emotional Problems N/A
Completed NCT03573167 - Mobile Phone-Based Motivational Interviewing in Kenya N/A
Completed NCT04817410 - ED Initiated Oral Naltrexone for AUD Phase 1
Active, not recruiting NCT04267692 - Harm Reduction Talking Circles for American Indians and Alaska Natives With Alcohol Use Disorders N/A
Completed NCT03872128 - The Role of Neuroactive Steroids in Stress, Alcohol Craving and Alcohol Use in Alcohol Use Disorders Phase 1
Completed NCT02989662 - INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers Phase 1/Phase 2
Recruiting NCT06030154 - Amplification of Positivity for Alcohol Use N/A
Active, not recruiting NCT05419128 - Family-focused vs. Drinker-focused Smartphone Interventions to Reduce Drinking-related Consequences of COVID-19 N/A
Completed NCT04564807 - Testing an Online Insomnia Intervention N/A
Completed NCT04284813 - Families With Substance Use and Psychosis: A Pilot Study N/A
Completed NCT04203966 - Mental Health and Well-being of People Who Seek Help From Their Member of Parliament
Recruiting NCT05861843 - Craving Assessment in Patients With Alcohol Use Disorder Using Virtual Reality Exposure
Terminated NCT04404712 - FAAH Availability in Psychiatric Disorders: A PET Study Early Phase 1
Enrolling by invitation NCT04128761 - Decreasing the Temporal Window in Individuals With Alcohol Use Disorder N/A
Not yet recruiting NCT06163651 - Evaluating a One-Year Version of the Parent-Child Assistance Program N/A
Not yet recruiting NCT06444243 - Psilocybin-assisted Therapy for Alcohol Use Disorder Phase 2
Not yet recruiting NCT06337721 - Preventing Alcohol Use Disorders and Alcohol-Related Harms in Pacific Islander Young Adults N/A
Enrolling by invitation NCT02544581 - Preliminary Analysis of the Soberlink Alcohol Breath Analyzer System's (SABA) Clinical Utility During Aftercare N/A