ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01852331
Recruitment Status : Completed
First Posted : May 13, 2013
Last Update Posted : May 7, 2015
Sponsor:
Collaborators:
Kowloon Hospital, Hong Kong
Queen Mary Hospital, Hong Kong
Capital Medical University
Xijing Hospital
Information provided by (Responsible Party):
Prof. Zhang Zhang-Jin, The University of Hong Kong

May 6, 2013
May 13, 2013
May 7, 2015
January 2013
April 2014   (Final data collection date for primary outcome measure)
  • Changes from baseline Positive and Negative Syndrome Scale (PANSS) at 8 weeks and 16 weeks [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: baseline, week 8 and week 16 ]
    The abnormal involuntary movement scale (AIMS) will be used to evaluate antipsychotic-induced abnormal involuntary movement symptoms.
Same as current
Complete list of historical versions of study NCT01852331 on ClinicalTrials.gov Archive Site
  • Change from baseline scores of Prolactin Related Adverse Event Questionnaire (PRAEQ) at 8 weeks and 16 weeks [ Time Frame: 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 [ Time Frame: baseline, week 8 and week 16 ]
    Other adverse effects will be assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU).
Same as current
  • Changes from baseline serum prolactin levels at 8 weeks and 16 weeks [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: baseline, week 8 and week 16 ]
    Serum concentrations of testosterone will be measured using chemiluminescent immunoassay (CLIA).
Same as current
 
Peony-Glycyrrhiza Decoction (PGD) for Antipsychotic-induced Hyperprolactinemia in Patients With Schizophrenia
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Schizophrenic Disorder
  • Hyperprolactinemia
  • Hyperprolactinaemia
  • 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.
  • Drug: Placebo
    The placebo granules are prepared to be identical to PGD granules in smell, taste and color.
  • 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.
    Intervention: Drug: PGD granules
  • 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.
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
103
118
November 2014
April 2014   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: Female
18 Years to 60 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
China
 
 
NCT01852331
UW 11-274
Yes
Not Provided
Not Provided
Prof. Zhang Zhang-Jin, The University of Hong Kong
The University of Hong Kong
  • Kowloon Hospital, Hong Kong
  • Queen Mary Hospital, Hong Kong
  • Capital Medical University
  • Xijing Hospital
Principal Investigator: Zhang-Jin Zhang, MMed, PhD School of Chinese Medicine, The University of Hong Kong
The University of Hong Kong
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP