search
Back to results

Peony-Glycyrrhiza Decoction (PGD) for Antipsychotic-induced Hyperprolactinemia in Patients With Schizophrenia (PGD-RCT)

Primary Purpose

Schizophrenia, Schizophrenic Disorder, Hyperprolactinemia

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PGD granules
Placebo
Sponsored by
The University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Schizophrenic Disorder, Hyperprolactinemia, Hyperprolactinaemia, Chinese herbal medicine, Traditional Chinese medicine, Peony-Glycyrrhiza Decoction, PGD, Glycyrrhiza Radix, Liquorice Root, Gancao, Paeoniae Alba Radix, White Peony Root, Baishao

Eligibility Criteria

18 Years - 60 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • have a primary diagnosis of schizophrenia or schizoaffective disorder based on International Classification of Diseases (10th edition);
  • under antipsychotic medications for at least three months and current conditions are stable, indicated by no difficulty to communicate with investigators and give informed consent;
  • have developed at least one overt hyperPRL-associated symptom, including oligomenorrhoea (infrequent, irregularly timed episodes of bleeding occurring at intervals of more than 35 days from the previous menstrual cycle), amenorrhoea (the absence of menstruation for three menstrual cycles or 6 months), galactorrhea, decreased libido, anorgasmia or erectile dysfunction; and
  • serum PRL levels are >24 ng/ml (or 1043.472 pmol/l) in female or >19 ng/ml (or 826.082 pmol/l) in male.

Exclusion Criteria:

  • unstable medical conditions;
  • suicidal ideas or attempts or aggressive behavior;
  • history of alcoholism in the past one year, characterized by compulsive and uncontrolled consumption of alcohol, despite the realization of its negative effects on health, relationship, and social standing;
  • history of drug abuse in past one year;
  • currently treated with Chinese medicine or other natural products;
  • allergic history of herbal medicine;
  • pre-existing hyperPRL symptoms not associated with antipsychotic treatment; and
  • pregnant and lactating women and those who refuse to use contraception during the study.

Sites / Locations

  • Xijing Hospital
  • Beijing Anding Hospital
  • Department of Psychiatry, Queen Mary Hospital
  • Department of Psychiatry, Kowloon Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

PGD granules

Placebo

Arm Description

While continuing current antipsychotic medications, subjects will receive adjunctive Peony-Glycyrrhiza Decoction (PGD) granules (equivalent to 45 g raw materials in total per day). They need to take the granules two times a day, each time one sachet (aluminum foil pack of 9g, tear open and empty contents into a cup, add 200ml hot water, stir until dissolute completely, and drink the preparation when warm), for a consecutive of 16 weeks.

While continuing current antipsychotic medications, subjects will receive adjunctive treatment with placebo granules. They need to take the placebo granules two times a day, each time one sachet (aluminum foil pack of 9g, tear open and empty contents into a cup, add 200ml hot water, stir until dissolute completely, and drink the preparation when warm), for a consecutive of 16 weeks.

Outcomes

Primary Outcome Measures

Changes from baseline Positive and Negative Syndrome Scale (PANSS) at 8 weeks and 16 weeks
The severity of psychotic symptoms will be assessed using the Positive and Negative Syndrome Scale (PANSS)
Changes from baseline Clinical Global Impression (CGI) score at 8 weeks and 16 weeks
The severity of psychotic symptoms will be assessed using the Clinical Global Impression (CGI).
Changes from baseline Simpson-Angus Rating Scale (SAS) at 8 weeks and 16 weeks
The Simpson-Angus Rating Scale (SAS) will be used to evaluate antipsychotic-induced abnormal involuntary movement symptoms.
Changes from baseline Abnormal involuntary movement scale (AIMS) at 8 weeks and 16 weeks
The abnormal involuntary movement scale (AIMS) will be used to evaluate antipsychotic-induced abnormal involuntary movement symptoms.

Secondary Outcome Measures

Change from baseline scores of Prolactin Related Adverse Event Questionnaire (PRAEQ) at 8 weeks and 16 weeks
Menstrual disturbances, breast symptoms and penile function will be assessed using the Prolactin Related Adverse Event Questionnaire (PRAEQ).
Change from baseline scores of Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at 8 weeks and 16 weeks
Other adverse effects will be assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU).

Full Information

First Posted
May 6, 2013
Last Updated
May 6, 2015
Sponsor
The University of Hong Kong
Collaborators
Kowloon Hospital, Hong Kong, Queen Mary Hospital, Hong Kong, Capital Medical University, Xijing Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT01852331
Brief Title
Peony-Glycyrrhiza Decoction (PGD) for Antipsychotic-induced Hyperprolactinemia in Patients With Schizophrenia
Acronym
PGD-RCT
Official Title
The Herbal Medicine Peony-Glycyrrhiza Decoction (PGD) as an Adjunctive Therapy to Treat Antipsychotic-induced Hyperprolactinemia in Patients With Schizophrenia: a Double-blind, Randomized, Placebo-controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Hong Kong
Collaborators
Kowloon Hospital, Hong Kong, Queen Mary Hospital, Hong Kong, Capital Medical University, Xijing Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators hypothesize that Peony-Glycyrrhiza Decoction (PGD) adjunctive therapy could reduce the incidence of prolactin (PRL)-related adverse events in patients with schizophrenia and suppress antipsychotic-induced elevation of PRL levels. This is a placebo-controlled trial conducted in schizophrenic patients to determine whether PGD adjunctive treatment could produce greater biochemical and clinical improvement on hyperprolactinemia (hyperPRL) compared to placebo treatment.
Detailed Description
Schizophrenia is a severe mental illness that affects 0.7-1.1% of the worldwide population. Most patients who develop a chronic course with frequent relapses and exacerbation of psychosis are required to have long-term treatment. The clinical outcomes of antipsychotic pharmacotherapy are limited, largely due to various adverse side effects. Hyperprolactinemia (hyperPRL) is the most challenging among them. Dopamine agonists may be used for hyperPRL if it does not improve after the reduction of antipsychotic doses. However, this may aggravate psychosis and abnormal involuntary movements, which may be a greater risk than hyperPRL itself. Chinese herbal medicine called Peony-Glycyrrhiza Decoction (PGD) has been widely introduced into the treatment of various conditions associated with hyperPRL in China and Japan. In our series of in-vitro experience it was found that PGD can significantly suppress PRL concentration in the cultured medium in a dose-dependent manner. Our recent open-labelled pilot study demonstrated that PGD significantly suppressed risperidone-induced elevation of blood PRL levels and produced a greater improvement on hyperPRL-related symptoms compared to dopamine agonist bromocriptine. Empirical and experimental evidence also confirmed that PGD and its individual herbal preparations possess a high safety profile. The encouraging results obtained from our laboratory and clinical pilot studies, together with findings of previous studies, have warranted an extensive controlled trial to further determine PGD as an effective therapy for the treatment of antipsychotic-induced hyperPRL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizophrenic Disorder, Hyperprolactinemia, Hyperprolactinaemia
Keywords
Schizophrenia, Schizophrenic Disorder, Hyperprolactinemia, Hyperprolactinaemia, Chinese herbal medicine, Traditional Chinese medicine, Peony-Glycyrrhiza Decoction, PGD, Glycyrrhiza Radix, Liquorice Root, Gancao, Paeoniae Alba Radix, White Peony Root, Baishao

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
103 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PGD granules
Arm Type
Active Comparator
Arm Description
While continuing current antipsychotic medications, subjects will receive adjunctive Peony-Glycyrrhiza Decoction (PGD) granules (equivalent to 45 g raw materials in total per day). They need to take the granules two times a day, each time one sachet (aluminum foil pack of 9g, tear open and empty contents into a cup, add 200ml hot water, stir until dissolute completely, and drink the preparation when warm), for a consecutive of 16 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
While continuing current antipsychotic medications, subjects will receive adjunctive treatment with placebo granules. They need to take the placebo granules two times a day, each time one sachet (aluminum foil pack of 9g, tear open and empty contents into a cup, add 200ml hot water, stir until dissolute completely, and drink the preparation when warm), for a consecutive of 16 weeks.
Intervention Type
Drug
Intervention Name(s)
PGD granules
Intervention Description
The preparation of Peony-Glycyrrhiza Decoction (PGD) granules is in compliance with Pharmacopoeia of the People's Republic of China and Good Manufacturing Practice (GMP). Briefly, sliced, broiled Paeoniae Alba Radix and Glycyrrhizae Radix in a ratio of 1:1 in weight will be immersed and boiled in an 8-fold volume of distilled water for 2.5 hours. This process will be repeated twice. The extract solution will be pooled and concentrated into granule form. Weight of the resulting granules contained in two 9g-sachet packs (to be taken in one day) is equivalent to 45 g raw herbal materials which are supplied for one day.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The placebo granules are prepared to be identical to PGD granules in smell, taste and color.
Primary Outcome Measure Information:
Title
Changes from baseline Positive and Negative Syndrome Scale (PANSS) at 8 weeks and 16 weeks
Description
The severity of psychotic symptoms will be assessed using the Positive and Negative Syndrome Scale (PANSS)
Time Frame
baseline, week 8 and week 16
Title
Changes from baseline Clinical Global Impression (CGI) score at 8 weeks and 16 weeks
Description
The severity of psychotic symptoms will be assessed using the Clinical Global Impression (CGI).
Time Frame
baseline, week 8 and week 16
Title
Changes from baseline Simpson-Angus Rating Scale (SAS) at 8 weeks and 16 weeks
Description
The Simpson-Angus Rating Scale (SAS) will be used to evaluate antipsychotic-induced abnormal involuntary movement symptoms.
Time Frame
baseline, week 8 and week 16
Title
Changes from baseline Abnormal involuntary movement scale (AIMS) at 8 weeks and 16 weeks
Description
The abnormal involuntary movement scale (AIMS) will be used to evaluate antipsychotic-induced abnormal involuntary movement symptoms.
Time Frame
baseline, week 8 and week 16
Secondary Outcome Measure Information:
Title
Change from baseline scores of Prolactin Related Adverse Event Questionnaire (PRAEQ) at 8 weeks and 16 weeks
Description
Menstrual disturbances, breast symptoms and penile function will be assessed using the Prolactin Related Adverse Event Questionnaire (PRAEQ).
Time Frame
baseline, week 8 and week 16
Title
Change from baseline scores of Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at 8 weeks and 16 weeks
Description
Other adverse effects will be assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU).
Time Frame
baseline, week 8 and week 16
Other Pre-specified Outcome Measures:
Title
Changes from baseline serum prolactin levels at 8 weeks and 16 weeks
Description
Serum concentrations of serum prolactin will be measured using chemiluminescent immunoassay (CLIA).
Time Frame
baseline, week 8 and week 16
Title
Changes from baseline serum estradiol levels at 8 weeks and 16 weeks
Description
Serum concentrations of estradiol will be measured using chemiluminescent immunoassay (CLIA).
Time Frame
baseline, week 8 and week 16
Title
Changes from baseline serum testosterone levels at 8 weeks and 16 weeks
Description
Serum concentrations of testosterone will be measured using chemiluminescent immunoassay (CLIA).
Time Frame
baseline, week 8 and week 16

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: have a primary diagnosis of schizophrenia or schizoaffective disorder based on International Classification of Diseases (10th edition); under antipsychotic medications for at least three months and current conditions are stable, indicated by no difficulty to communicate with investigators and give informed consent; have developed at least one overt hyperPRL-associated symptom, including oligomenorrhoea (infrequent, irregularly timed episodes of bleeding occurring at intervals of more than 35 days from the previous menstrual cycle), amenorrhoea (the absence of menstruation for three menstrual cycles or 6 months), galactorrhea, decreased libido, anorgasmia or erectile dysfunction; and serum PRL levels are >24 ng/ml (or 1043.472 pmol/l) in female or >19 ng/ml (or 826.082 pmol/l) in male. Exclusion Criteria: unstable medical conditions; suicidal ideas or attempts or aggressive behavior; history of alcoholism in the past one year, characterized by compulsive and uncontrolled consumption of alcohol, despite the realization of its negative effects on health, relationship, and social standing; history of drug abuse in past one year; currently treated with Chinese medicine or other natural products; allergic history of herbal medicine; pre-existing hyperPRL symptoms not associated with antipsychotic treatment; and pregnant and lactating women and those who refuse to use contraception during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhang-Jin Zhang, MMed, PhD
Organizational Affiliation
School of Chinese Medicine, The University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Xijing Hospital
City
Xian
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Facility Name
Beijing Anding Hospital
City
Beijing
ZIP/Postal Code
100088
Country
China
Facility Name
Department of Psychiatry, Queen Mary Hospital
City
Hong Kong
Country
China
Facility Name
Department of Psychiatry, Kowloon Hospital
City
Kowloon
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
27755159
Citation
Man SC, Li XB, Wang HH, Yuan HN, Wang HN, Zhang RG, Tan QR, Wong HK, McAlonan GM, Wang CY, Zhang ZJ. Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial. J Clin Psychopharmacol. 2016 Dec;36(6):572-579. doi: 10.1097/JCP.0000000000000607.
Results Reference
derived

Learn more about this trial

Peony-Glycyrrhiza Decoction (PGD) for Antipsychotic-induced Hyperprolactinemia in Patients With Schizophrenia

We'll reach out to this number within 24 hrs