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

NCT ID: NCT01852331

Last Updated: 2015-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2014-11-30

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.

Conditions

Schizophrenia; Schizophrenic Disorder; Hyperprolactinemia; Hyperprolactinaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

PGD granules

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Kowloon Hospital, Hong Kong

OTHER

Sponsor Role: collaborator

Queen Mary Hospital, Hong Kong

OTHER

Sponsor Role: collaborator

Capital Medical University

OTHER

Sponsor Role: collaborator

Xijing Hospital

OTHER

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Prof. Zhang Zhang-Jin

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhang-Jin Zhang, MMed, PhD

Role: PRINCIPAL_INVESTIGATOR

School of Chinese Medicine, The University of Hong Kong

Locations

Xijing Hospital

Xian, Shanxi, China

Beijing Anding Hospital

Beijing, , China

Department of Psychiatry, Queen Mary Hospital

Hong Kong, , China

Department of Psychiatry, Kowloon Hospital

Kowloon, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 27755159 (View on PubMed)

Other Identifiers

UW 11-274

Identifier Type: -

Identifier Source: org_study_id