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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by The University of Hong Kong
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
ClinicalTrials.gov Identifier:
NCT01852331
First received: May 6, 2013
Last updated: May 10, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Schizophrenia
Schizophrenic Disorder
Hyperprolactinemia
Hyperprolactinaemia
Drug: PGD granules
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • Changes from baseline Positive and Negative Syndrome Scale (PANSS) at 8 weeks and 16 weeks [ Time Frame: baseline, week 8 and week 16 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline, week 8 and week 16 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: baseline, week 8 and week 16 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Serum concentrations of testosterone will be measured using chemiluminescent immunoassay (CLIA).


Estimated Enrollment: 118
Study Start Date: February 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852331

Contacts
Contact: Zhang-Jin ZHANG, MMed, PhD +85225890445 zhangzj@hkucc.hku.hk
Contact: Sui-Cheung Man, BCM, BSc +85225890466 marksman@hku.hk

Locations
China, Shanxi
Xijing Hospital Not yet recruiting
Xian, Shanxi, China, 710032
Contact: Qing-Rong TAN, MSc    +862984775507    tanqingrong@gmail.com   
Principal Investigator: Qing-Rong TAN, MSc         
China
Beijing Anding Hospital Recruiting
Beijing, China, 100088
Contact: Chuan-Yue WANG, MD    +861058303198    wang.cy@vip.tom.com   
Principal Investigator: Chuan-Yue WANG, MD         
Department of Psychiatry, Queen Mary Hospital Not yet recruiting
Hong Kong, China
Contact: Yu-Hai, Eric CHEN, MBChB, MD    +85222554488    eyhchen@hku.hk   
Principal Investigator: Yu-Hai, Eric CHEN, MBChB, MD         
Department of Psychiatry, Kowloon Hospital Not yet recruiting
Kowloon, China
Contact: Roger NG, MBChB, MSc    +85231296432    ngmk@ha.org.hk   
Principal Investigator: Roger NG, MBChB, MSc         
Sponsors and Collaborators
The University of Hong Kong
Kowloon Hospital, Hong Kong
Queen Mary Hospital, Hong Kong
Capital Medical University
Xijing Hospital
Investigators
Principal Investigator: Zhang-Jin Zhang, MMed, PhD School of Chinese Medicine, The University of Hong Kong
  More Information

No publications provided

Responsible Party: Prof. Zhang Zhang-Jin, Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT01852331     History of Changes
Other Study ID Numbers: UW 11-274
Study First Received: May 6, 2013
Last Updated: May 10, 2013
Health Authority: Hong Kong: Department of Health

Keywords provided by The University of Hong Kong:
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

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Hyperprolactinemia
Mental Disorders
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on October 01, 2014