Clinical Study of Ligustrazine in Treating Alcohol Addiction

Sponsor

Shenzhen Kangning Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05942352

Collaborator

(none)

400

Enrollment

Location

Arms

Anticipated Duration (Months)

33.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Alcohol consumption is one of the most important risk factors for chronic non-communicable diseases in the population, and it is also the main cause of death from cancer, cardiovascular disease and lung disease, causing serious health, economic and social problems. The current alcohol-abstinence drugs have limited therapeutic effects and still present a high relapse rate. It is an urgent need to develop effective drugs for the treatment of alcohol addiction. The multimodal mechanism of action of ligustrazine in the central nervous system indicates that ligustrazine is expected to be developed as a potential therapeutic drug for alcohol addiction. Our study investigated the therapeutic effect of ligustrazine on subjects with alcohol addiction and the mechanism of multimodal brain imaging by administering ligustrazine, in order to develop new targeted drugs for alcohol treatment and provide more effective diagnosis and treatment methods for clinical treatment.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Abuse Arteriosclerosis	Drug: Ligustrazine by intravenously administration Drug: Ligustrazine by mouth Drug: Placebo by intravenously administration Drug: Placebo by mouth	Phase 4

Detailed Description

Background: Alcohol use disorders (AUD) is a common chronic disease with great harm to society, causing a huge disease burden and social burden. In recent years, a lot of progress has been made in the field of drug abuse in the field of neurobiology, but it is difficult to apply it to AUD. The clinical treatment of alcohol addiction has always been under the predicament of lack of medicine and drugs, and the development of new therapeutic intervention methods is urgently needed. Although the neurobiological mechanism of ligustrazine's efficacy is still unclear, its multimodal mechanism of action in the central nervous system suggests that ligustrazine is expected to be developed as a potential therapeutic drug for alcohol addiction. Objective: This study intends to develop a therapeutic drug that can effectively relieve alcohol withdrawal syndrome, promote the disappearance of addictive behaviors, and effectively prevent re-drinking for the main active ingredient ligustrazine of the traditional Chinese medicine Ligusticum chuanxiong. The implementation of this project will help to expand the new functions (new indications) of traditional Chinese medicine and its main active ingredient ligustrazine, which may be developed into an effective drug for the treatment of alcohol addiction, and explore its neuroimaging mechanism. METHODS: Eligible alcohol addiction cases were recruited and assigned to 3 treatment groups according to randomized double-blind procedure (conventional treatment

placebo control group, conventional treatment + ligustrazine short-term treatment group, conventional treatment + ligustrazine maintenance treatment group ; about 100 cases in each group). After 15 days of group treatment, follow-up for 1 year, observe and compare the relapse rate of alcohol addiction, the duration of abstinence (days), the frequency and amount of drinking, the degree of craving, and other cognitive and psychological changes in each group, and record adverse reactions. Clinical efficacy and safety of ligustrazine on alcohol addiction. The changes of multimodal brain imaging in each group were analyzed, and the neural effects of ligustrazine treatment were explored. ②Recruit healthy controls ≥ 100 cases, match the sex and age with the cases, collect cognitive psychological indicators and brain imaging data at baseline and 1 year after baseline, and compare them in parallel with each treatment group to explore the treatment of alcohol addiction with Ligustrazine neural mechanism.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Clinical Study of Ligustrazine in Treating Alcohol Addiction

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Enrolled participants would accept intravenous administration of 250ml saline per day for 15 days, then 50 mg placebo tablet by mouth would be maintained for 1 year.	Drug: Placebo by intravenously administration Intravenous administration of 250ml saline per day for 15 days Other Names: Saline by intravenously administration Drug: Placebo by mouth 50 mg placebo tablet by mouth would be maintained for 1 year Other Names: Starch tablet by mouth
Experimental: Ligustrazine short-term treatment Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days. Then, a 50 mg placebo tablet by mouth would be maintained for 1 year	Drug: Ligustrazine by intravenously administration Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days Other Names: Tetramethylpyrazine by intravenously administration Drug: Placebo by mouth 50 mg placebo tablet by mouth would be maintained for 1 year Other Names: Starch tablet by mouth
Experimental: Ligustrazine maintenance treatment Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days，then, a 50 mg Ligustrazine tablet by mouth would be maintained for 1 year.	Drug: Ligustrazine by intravenously administration Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days Other Names: Tetramethylpyrazine by intravenously administration Drug: Ligustrazine by mouth 50 mg Ligustrazine tablet by mouth would be maintained for 1 year Other Names: Tetramethylpyrazine by mouth

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Enrolled participants would accept intravenous administration of 250ml saline per day for 15 days, then 50 mg placebo tablet by mouth would be maintained for 1 year.

Drug: Placebo by intravenously administration

Intravenous administration of 250ml saline per day for 15 days

Other Names:

Saline by intravenously administration

Drug: Placebo by mouth

50 mg placebo tablet by mouth would be maintained for 1 year

Other Names:

Starch tablet by mouth

Experimental: Ligustrazine short-term treatment

Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days. Then, a 50 mg placebo tablet by mouth would be maintained for 1 year

Drug: Ligustrazine by intravenously administration

Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days

Other Names:

Tetramethylpyrazine by intravenously administration

Drug: Placebo by mouth

50 mg placebo tablet by mouth would be maintained for 1 year

Other Names:

Starch tablet by mouth

Experimental: Ligustrazine maintenance treatment

Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days，then, a 50 mg Ligustrazine tablet by mouth would be maintained for 1 year.

Drug: Ligustrazine by intravenously administration

Ligustrazine hydrochloride was administered intravenously by dissolving 40mg in 250ml saline per day for 15 days

Other Names:

Tetramethylpyrazine by intravenously administration

Drug: Ligustrazine by mouth

50 mg Ligustrazine tablet by mouth would be maintained for 1 year

Other Names:

Tetramethylpyrazine by mouth

Outcome Measures

Primary Outcome Measures

Relapse rate [Four week after treatment]
Percentage of participants who relapse by assuming that drinking alcohol on more than 3 days in a month in an unrestricted environment is re-drinking

Secondary Outcome Measures

Time to maintain abstinence [Four week after treatment]
Measurement of exactly time(days) to maintain abstinence
Frequency of alcohol consumed [Four week after treatment]
Assessment of frequency to consume alcohol
Amount of alcohol consumed [Four week after treatment]
The amount of alcohol consumed would be measured.
Change from baseline in alcohol craving by using Visual Analog Scale of Alcohol Craving at week 4. [Four week after treatment]
Alcohol-specific Visual Analog Scale is a valid measurements of craving for a alcohol. Possible scores range from 0 (no craving) to 10 (want to drink imediately). Change= (week 4 score - baseline score)
Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores [Four week after treatment]
BOLD fMRI signals evaluate different brain ROI

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Alcohol addiction:

①Aged 18~65 years old;

② Meet the diagnostic criteria of DSM-IV alcohol dependence;

③No clear history of neurological diseases in the past, no family history of mental diseases;

④Voluntary participation in research, with good follow-up and observation, and good compliance;

⑤ No obvious psychotic symptoms.

Combined with the treatment indications of ligustrazine, the selected cases must meet the arteriosclerosis index ≥ 4:

Arteriosclerosis index (AI) = [total cholesterol (TC) - high-density lipoprotein (HDL)] ÷ high-density lipoprotein (HDL), the normal value of AI is <4, reflecting that the degree of arteriosclerosis is not serious or mild, The smaller the value, the lighter the degree of arteriosclerosis. If the arteriosclerosis index ≥ 4, it means that obvious arteriosclerosis has occurred, and the larger the value, the more serious the degree of arteriosclerosis.

Exclusion Criteria:

① Acute alcohol withdrawal phase, CIWA-Ar > 9 points;
Severe neurological or mental diseases caused by diseases other than chronic alcohol dependence: such as stroke, intracranial infection, brain tumor, schizophrenia, etc.;
Have experienced traumatic brain injury or other damage to brain tissue; ④ Taking any other psychotropic drugs, drug use or other substance dependence in the short term; ⑤ There are contraindications to the application of ligustrazine, or women are pregnant and other conditions that are not suitable for drug use; ⑥ There are conditions that are not suitable for head MRI examination, such as claustrophobia, metal objects in the body, etc.