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

Sponsor

The University of Hong Kong (Other)

Overall Status

Completed

CT.gov ID

NCT01852331

Collaborator

Kowloon Hospital, Hong Kong (Other), Queen Mary Hospital, Hong Kong (Other), Capital Medical University (Other), Xijing Hospital (Other)

103

Enrollment

Locations

Arms

Duration (Months)

25.8

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizophrenic Disorder Hyperprolactinemia Hyperprolactinaemia	Drug: PGD granules Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

103 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PGD granules 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.	Drug: PGD granules 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.
Placebo Comparator: Placebo 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.	Drug: Placebo The placebo granules are prepared to be identical to PGD granules in smell, taste and color.

Arm

Intervention/Treatment

Active Comparator: PGD granules

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.

Drug: PGD granules

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.

Placebo Comparator: Placebo

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.

Drug: Placebo

The placebo granules are prepared to be identical to PGD granules in smell, taste and color.

Outcome Measures

Primary Outcome Measures

Changes from baseline Positive and Negative Syndrome Scale (PANSS) at 8 weeks and 16 weeks [baseline, week 8 and week 16]
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 [baseline, week 8 and week 16]
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 [baseline, week 8 and week 16]
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 [baseline, week 8 and week 16]
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 [baseline, week 8 and week 16]
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 [baseline, week 8 and week 16]
Other adverse effects will be assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU).

Other Outcome Measures

Changes from baseline serum prolactin levels at 8 weeks and 16 weeks [baseline, week 8 and week 16]
Serum concentrations of serum prolactin will be measured using chemiluminescent immunoassay (CLIA).
Changes from baseline serum estradiol levels at 8 weeks and 16 weeks [baseline, week 8 and week 16]
Serum concentrations of estradiol will be measured using chemiluminescent immunoassay (CLIA).
Changes from baseline serum testosterone levels at 8 weeks and 16 weeks [baseline, week 8 and week 16]
Serum concentrations of testosterone will be measured using chemiluminescent immunoassay (CLIA).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xijing Hospital	Xian	Shanxi	China	710032
2	Beijing Anding Hospital	Beijing		China	100088
3	Department of Psychiatry, Queen Mary Hospital	Hong Kong		China
4	Department of Psychiatry, Kowloon Hospital	Kowloon		China