Efficacy and Safety of Peropirone Hydrochloride Tablets in the Treatment of Adolescent Bipolar Disorder Depression

Objective to Evaluate the Efficacy and Safety of Peropirone Hydrochloride Tablets in the Treatment of Adolescent Bipolar Depressive Episode: a Multicenter Open Randomized Controlled Clinical Trial

Bipolar disorder, a type of mood disorder that occurs in various forms, such as depression, mania, hypomania or irregularity.According to the World Health Organization mental health survey, the lifetime prevalence of bipolar disorder is 2.4%; the 12-month prevalence was 1.5%. The lifetime incidence in Shenzhen was 1.5%, and the 12-month incidence was 1.1%. In another study in Hong Kong, the 12-month prevalence of bipolar I, II, and "soft" II was 1.4%, 0.5%, and 1.8%, respectively. Due to endocrine effects, bipolar disorder is more common in women than men, and mainly occurs in late adolescence and early adulthood, with an early trend. An investigation involving 23 countries around the world found that the average age of onset of bipolar disorder was 25 years old, and the low age group (17.24±3.20 years old) accounted for 41.7%. Another study in the United States showed that the average age of onset of bipolar disorder was 20 years old, and the low age group (14.5±4.9 years old) accounted for 63%. With the improvement of medical level, the diagnosis rate of bipolar disorder is getting closer to the true prevalence rate.

Without active treatment, the symptoms of bipolar disorder, especially depression, will accompany the patients for a long time. The quality of life of patients is seriously affected.

The safety of piperopilon hydrochloride has been widely recognized from pre-market clinical research to post-market clinical practice. A total of a clinical study involving 1191 patients showed that the incidence of side effects from long-term use of piperopilone was 21.3%, and the main side effects were mild in the nervous and digestive systems. In addition, it has been reported that piperopirone is also safe and effective for adolescents.Therefore, the investigators designed this study to explore the atypical antipsychotic drug piperopirone as a monotherapy or in combination with mood stabilizer.Clinical efficacy and safety of lithium acid in the treatment of depressive episodes in adolescents with bipolar disorder, and its improvement in cognitive function were assessed.The goal is to evaluate the efficacy and safety of piperopilone hydrochloride tablets in the treatment of bipolar depressive episode in adolescents.

Study Overview

• Status: Unknown
• Conditions: Depressive Disorder
• Intervention / Treatment: Drug: Lithium Carbonate Pill; Drug: Perospirone hydrochloride tablets; Drug: Lithium carbonate + perospirone hydrochloride

Detailed Description

Participants will be randomly assigned to the lithium carbonate group, piperopirone hydrochloride group or the lithium carbonate + Piperopirone hydrochloride group after obtaining the corresponding random number according to the order of inclusion. According to the random centers, the lithium carbonate group: piperopirone hydrochloride group: lithium carbonate + Piperopirone hydrochloride group was 1:1:1

• Study Type: Interventional
• Enrollment (Anticipated): 189
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
      • Contact: Yiru Fang, M.D., Ph.D.; Phone Number: (86) 18017311133; Email: yirufang@gmail.com
      • Principal Investigator: Yiru Fang, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatients or inpatients who met the diagnostic criteria of DSM-5 or ICD-10 for depressive episode of bipolar disorder.
2. Willing to participate in clinical research and sign informed consent
3. 12 ≤ age ≤ 18
4. HAMD-17 score ≥ 17; HAMD-17 item 1 (depression) ≥ 2, and YMRS ≤ 12
5. Physical examination, laboratory examination, vital signs and 12 lead ECG showed that the physical condition was stable. If any test results are beyond the normal range, they can be included only if they are judged to be abnormal or deviated from the normal values but have no clinical significance or belong to reasonable conditions in the study population. Such decisions must be recorded in the subject's original file and signed by the researcher

Exclusion Criteria:

1. Besides bipolar disorder, the diagnosis includes schizophrenia, schizophrenic affective disorder, schizoid disorder, depression, dissociation disorder, borderline personality disorder, material dependence, autism, organic mental disease, etc
2. Other conditions except bipolar disorder were diagnosed, such as schizophrenia, schizophrenic affective disorder, schizophrenia like disorder, depression, dissociation disorder, borderline personality disorder, material dependence, autism, organic mental disease, etc. according to the judgment of the researcher, the patient is at risk of suicide or injury to others, or HAMD-17 item 3 Score ≥ 3, or attempted suicide in the past six months
3. Patients with rapid circulation type;
4. Those who had suffered from serious heart, liver, brain, lung, kidney and other serious diseases in the past or at present, and the researchers considered that they were not suitable for the study;
5. The results of Biochemistry, hematology, electrocardiogram or urine test were not within the normal value range of the laboratory at the time of screening, and had clinical significance according to the judgment of the researchers (except for the abnormal indexes of reasonable condition in the research population, such as abnormal blood glucose and blood lipid indexes);
6. The subjects received electroconvulsive therapy (ECT) within 6 months before enrollment;
7. There was a history of malignant tumor or complications;
8. Known allergy history or complications to test drug or ingredient (with previous history of allergic reaction caused by drug, rash, urticaria, etc.);
9. Pregnant and lactating women and patients unable to take appropriate contraceptive measures during the trial period;
10. Patients with previous suicidal behavior or existing strong suicidal tendency and patients with serious excited and aggressive behavior.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lithium carbonate group; Lithium carbonate treatment, stable blood lithium concentration 0.5-1.2 mmol / L, course of 8 weeks.	Drug: Lithium Carbonate Pill; Lithium carbonate treatment, stable blood lithium concentration 0.5-1.2 mmol / L, course of 8 weeks.
Experimental: Perospirone hydrochloride group; The dosage of perospirone hydrochloride tablets was 16-36 mg / D for 8 weeks.	Drug: Perospirone hydrochloride tablets; The dosage of perospirone hydrochloride tablets was 16-36 mg / D for 8 weeks.
Experimental: Lithium carbonate + perospirone hydrochloride group; The stable blood lithium concentration was 0.5-1.2 mmol / L, and the dose of perospirone hydrochloride tablets was 16-36 mg / D for 8 weeks.	Drug: Lithium carbonate + perospirone hydrochloride; The stable blood lithium concentration was 0.5-1.2 mmol / L, and the dose of perospirone hydrochloride tablets was 16-36 mg / D for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression Scale-Bipolar Disorder Scale (CGI-BP-S) score	The investigators adopt the clinical General Impression Scale - Bipolar Disorder Scale (CGI-BP-S) score to analyze the scores of the subjects in different periods.	Change from baseline at 2,4,8 week.
Hamilton Depression Scale (HAMD-17) score	The investigators adopt the Hamilton Depression Scale (HAMD-17) score to judge the subjects' depression. Starting points: Hamilton Depression Scale (HAMD-17)) ≥2, clinical remission: Hamilton Depression Scale (HAMD-17)) <7.	Change from baseline at 2,4,8 week.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Young's Manic Rating Scale (YMRS) score	Young's Manic Rating Scale (YMRS) was used to determine the degree of mania in the subjects. Initial score: Young's Manic Rating Scale (YMRS) score ≤12; Clinical remission: Young's Manic Rating Scale (YMRS) score ≤5.	Change from baseline at 2,4,8 week.
Montreal Cognitive Assessment Scale (MoCA) score	The investigators adopt the Montreal cognitive assessment scale (MoCA) score to judge whether the subjects with normal cognition and affect its subsequent different drugs.	Change from baseline at 8 week.
Wisconsin Card Sorting Test (WCST-128) score	The investigators used the Wisconsin Card Sorting Test (WCST-128) score to determine whether the subjects had normal cognition. Reference value: total response number < 60: indicating cognitive abnormalities; Incorrect response number > 45: indicates cognitive abnormality	Change from baseline at 8 week.
WISC score for Children	WISC Score for Children was used to determine whether subjects' IQ was affected by their disease. Reference value: 1. Low: Total IQ score ≤90; 2. Normal: Total IQ score is 90-110; High IQ: total IQ score ≥110	Change from baseline at 8 week.

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Investigators: Principal Investigator: Yiru Fang, professor, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: January 31, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 31, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate; Perospirone
• Other Study ID Numbers: 3.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the trial is over, after obtaining the written consent of the sponsor, the research unit can publish the research results of this clinical trial in the form of a paper, but the source of the drug must be stated. The investigator of each research unit has the right to sign the paper. ponsors can also publish papers or use experimental content, or participate in signing
• IPD Sharing Time Frame: start from 2021.6.30,last for 2years
• IPD Sharing Access Criteria: the cooperative partners
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No