Clinical trial NCT01852331: Peony-Glycyrrhiza Decoction (PGD) for Antipsychotic-induced Hyperprolactinemia in Patients With Schizophrenia
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Kowloon Hospital, Hong Kong
name: Queen Mary Hospital, Hong Kong
name: Capital Medical University
name: Xijing Hospital
First posted: 2013-05-13
Enrollment: 103
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Changes from baseline Positive and Negative Syndrome Scale (PANSS) at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
measure: Changes from baseline Clinical Global Impression (CGI) score at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
measure: Changes from baseline Simpson-Angus Rating Scale (SAS) at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
measure: Changes from baseline Abnormal involuntary movement scale (AIMS) at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
Secondary outcomes:
measure: Change from baseline scores of Prolactin Related Adverse Event Questionnaire (PRAEQ) at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
measure: Change from baseline scores of Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
Other outcomes:
measure: Changes from baseline serum prolactin levels at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
measure: Changes from baseline serum estradiol levels at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
measure: Changes from baseline serum testosterone levels at 8 weeks and 16 weeks
timeFrame: baseline, week 8 and week 16
Locations:
city: Xian
country: China
facility: Xijing Hospital
state: Shanxi
city: Beijing
country: China
facility: Beijing Anding Hospital
city: Hong Kong
country: China
facility: Department of Psychiatry, Queen Mary Hospital
city: Kowloon
country: China
facility: Department of Psychiatry, Kowloon Hospital
Study officials:
affiliation: School of Chinese Medicine, The University of Hong Kong
name: Zhang-Jin Zhang, MMed, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.