The primary objective of this study is to assess tolerance and efficacy of 12 weeks BP1.3656 (30 µg or 60 µg OD versus placebo) to reduce alcohol consumption in alcohol dependent patients.
ID
Source
Brief title
Condition
- Psychiatric disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of the study is the decrease in number of monthly heavy
drinking days (HDD: * 60 g/day in men and * 40 g/day) form baseline to end of
the double blind randomization phase.
Secondary outcome
The secondary parameters in this study are:
* Total daily alcohol consumption (TAC: total alcohol consumption) from
baseline to end of treatment;
* Percent of patients without heavy drinking days during the 12 weeks
double-blind, randomized treatment (continuous controlled drinking= CCD);
* Percent of Abstinent Days during the 12 weeks double-blind, randomized
treatment (PAD: percent of abstinent days);
* Continuous Abstinence Duration during the 12 weeks double-blind, randomized
treatment (CAD: continuous abstinence duration);
* 4-week point prevalence abstinence at end of treatment;
* Improvement in alcohol biomarkers (e.g. ALAT, ASAT, % CDT) during the 12
weeks double-blind, randomized treatment;
* Craving (Obsessive Compulsive Drinking Scale) during the 12 weeks
double-blind, randomized treatment;
* Beck Depression Inventory (BDI) during the 12 weeks double-blind, randomized
treatment;
* Treatment retention during the 12 weeks double-blind, randomized treatment;
* Safety will be assessed by evaluation of treatment emergent adverse events
(TEAE), physical examinations, clinical laboratory tests (blood chemistry,
hematology and urinalysis), subsequent end of treatment potential withdrawal,
evaluation scales and physical examination, measurement of heart rat, blood
pressure and body weight at each study visit. If at ECG Fridericia's corrected
QT-interval *500 ms, or if difference to baseline is * 60ms, it will be
required to check ECG by second measurement.
Background summary
Alcohol use disorder remains a highly stigmatized, under-diagnosed and
under-treated disease. The current approved medications show inconsistent
success in reducing relapse or drinking. Because alcohol dependence is such a
common and devastating disease, there is an ongoing search for new treatments
that could be more effective and better tolerated. Therefore, the development
and testing of medications that target novel brain systems involved in alcohol
dependence is of acute interest to patients, clinicians and researchers.
Studies in rats suggest that the histamine H3 receptor inverse agonist BP1.3656
significantly decreases alcohol self-administration in alcohol dependent rats.
Moreover, BP1.3656 decreases reinstatement in alcohol dependent rats.
Study objective
The primary objective of this study is to assess tolerance and efficacy of 12
weeks BP1.3656 (30 µg or 60 µg OD versus placebo) to reduce alcohol consumption
in alcohol dependent patients.
Study design
The study starts as a multi-center, randomized, double-blind,
placebo-controlled trial with 12 weeks BP1.3656 (30µg of 60µg, OD) treatment
versus placebo to reduce alcohol consumption in patients with moderate to
severe DSM-5 alcohol use disorder. This randomized phase ends with a one week
single-blind placebo treatment. Total duration of the study is maximal 15 weeks:
* 2 weeks of screening, during which a screening and baseline visit are
performed;
* 12 weeks of double blind treatment phase, during which 5 visits are performed;
* 1 week of single blind treatment phase with placebo, during which one phone
contact is scheduled, concluded by a site visit.
Intervention
Beside treatment with the study medication (either placebo or active medication
BP1.3656 30 µg or 60 µg once daily, per os), patients have to follow cognitive
behavioral therapy (CBT) during the first 12 weeks of the study. Furthermore,
several neuropsychiatric questionnaires have to be completed both at start of
the study and during the study. It concerns the MINI, CIWA-Ar and AASE at the
start and the TLFB (as a patient diary), SF-12 Healt Survey, BDI, AUDIT, OCDS
and PSQI both at start and during the study.
Blood and urine samples will be collected to assess hematology, clinical
chemistry and serology (at screening and during final visit of double blind
phase) to assess alcohol biomarkers and liver function (at baseline, V2, 4 and
6).
Urine will be collected to measure ethyl glucuronide (EtG), an alcohol
metabolite (at baseline, V2, 4 and 6). Standard urinalysis will be done at
baseline, as well as a urine drug screen. At each visit, an alcohol breath test
will be done.
Study burden and risks
Both psychosocial support approaches and pharmacological agents are current
treatments for alcohol use disorder. Pharmacological treatment of patients with
an alcohol use disorder is needed to alleviate withdrawal symptoms, reduce
craving and prevent relapses. Several drugs are approved for the treatment of
alcohol use disorder, these compounds are all directed at full abstinence and
they all have side effects. Patients, while recognizing their alcohol problem,
are unable or unwilling to completely stop consuming alcohol, leading to an
inevitable deterioration over time of their psycho-physical state and social
relationships. Reduction may be an opportunity to prepare the individual for
achieving complete abstinence (the ultimate goal). Reduction of alcohol
consumption could be achieved by using BP1.3656, taken once daily.
Reported side effects for BP1.3656 are insomnia, local reaction, rhinitis,
headache, pollakiuria (abnormally frequent urination), asthenia/somnolence,
respiratory disorders, disturbance in attention, gastroenteritis (inflammation
of bowel), hot flush, musculoskeletal stiffness, nasopharyngitis, nausea,
tonsillitis, pain in extremity and sweats. These effects were all transient and
all resolved spontaneously when treatment was stopped.
The following study procedures will be performed:
* Physical examination at baseline and visit 6
* Vital signs at each site visit
* Recording of ECG at baseline, visit 2, 4 and 6.
Risks related to recording of ECGs can be redness of skin caused by sticky pads.
* Completion of neuropsychiatric questionnaires. It concerns the MINI, CIWA-AR
and AASE at start of the study and the TLFB (as a patient diary), SF-12 Health
Survey (QoL), BDI, AUDIT, OCDS and PSQI at start and during the study. The
completion of questionnaires can result in psychological discomfort.
* Collection of blood to assess clinical chemistry, hematology and serology at
baseline and visit 6 (liver functions will be more frequently assessed). Risks
related to blood collection can be: fainting, redness, bruising, bleeding or
infection at puncture site.
rue Rameau 9
Paris 75002
FR
rue Rameau 9
Paris 75002
FR
Listed location countries
Age
Inclusion criteria
1. Male of female with moderate or severe DSM-5 alcohol use disorder (based on the alcohol use disorders section of the MINI plus);
2. Ages 18-65;
3. Low to moderate alcohol withdrawal symptoms: CIWA-Ar scale < 10 at baseline assessment;
4. Normal weight: 18 kg/m2 * 35 kg/m2;
5. Excessive alcohol use: number of heavy drinking days (* 60g/day in men and * 40 g/day in women) * 15 during 30 days prior to screening and * 7 during the 2 weeks between screening and baseline;
6. Treatment-seeking, treatment goal: reduced drinking or abstinence;
7. If fertile, both males and females must agree to use effective birth control, agree to continue this method for the duration of the study up until 21 days after study completion and be negative to serum pregnancy test performs at the screening visit. Females should not be breastfeeding.;
8. Adequate social support according to the investigator to comply with the study requirements described in the protocol (e.g. transportation to and from the trial site, self-rating scales, drug compliance, scheduled visits, etc.);
9. Voluntarily expressed willingness to participate in the study, understanding protocol procedues and having signed and dated an informed consent prior to the start of the protocol required procedures while not intoxicated (BAC < 0.05);
10. Willingness to receive psychosocial support.
Exclusion criteria
1. History of delirium tremens, epilepsy, or withdrawal seizures;
2. Clinical depression or suicidality; Beck Depression Inventory (BDI) * 16 and suicidality (item G * 0);
3. Recent illicit drug use, i.e. cannabis, cocaine, amphetamine or opiods;
4. Clinically significant cardiovascular, hematologic, severe hepatic impairment or (FLTs > 3 ULN), renal (stage 2 and 3 according to international classification of renal kidney disease), neurological, endocrinological abnormalities or abnormal clinical laboratory results (in most cases > 3 ULN)
5. History of serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes;
6. HIV positive; HCV postive; HBsAg postive;
7. History of psychosis, or current severe psychiatric disorder, e.g. schizophrenia, bipolar disorder, severe depression or organic brain syndrome unrelated to alcohol abuse;
8. Physical dependence on sedatives or hypnotics that requires pharmacologically supported detox;
9. Receiving ongoing alcohol use disorder medication (e.g. Baclofen);
10. Other active clinically significant illness, which could interfere with the study conduct or counter-indicate the study treatments or place the patient at risk during the trial or compromise the study participation, such as Parkinson*s disease;
11. Known history of syncope, arrhytmia, myocardial infarction or any known significant ECG abnormality;
12. Known hypersensitivity to the tested treatment including active substance and excipients;
13. Participation in clinical trials and receipt of investigational drug(s) during previous 60 days, except as explicitly approve by the principal investigator;
14. Insufficient medical insurance according to local regulations;
15. Pregnant woman or a pregnancy detected with a positive serum pregnancy test performed at the screening visit or lactating women;
16. Male subject who want to conceive a child during the duration of the study up until 21 days after study completion.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000069-57-NL |
| CCMO | NL61245.018.17 |