SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT02433717

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Study on the Efficacy, Pharmacokinetics and Adverse Effects of Paliperidone ER

Background Paliperidone is an active metabolite of risperidone, both of which are antipsychotic agents for treatment of schizophrenia and related psychotic disorders. Pharmacogenetic studies have revealed that the efficacy and side effects of antipsychotic agents are related to polymorphisms of specific genes, however, there are just a few related studies on paliperidone. The current study aims to evaluate whether pharmacogenetic markers related to risperidone and genetic markers associated with schizophrenia have effects on the clinical effectiveness of paliperidone treatment. The study also uses changes of event-related potentials (ERP) as indices for clinical efficacy. Methods It is a prospective, open-label, non-randomized and uncontrolled clinical trial to study the efficacy and side effects of 6-week paliperidone ER treatment for patients with schizophrenia or schizoaffective disorder. The first three weeks of treatment has to be inpatient treatment. In the first two weeks, participants will take 9 mg paliperidone ER daily. Then the dose of paliperidone can be adjusted to within the range of 6-12 mg per day. Efficacy indicators include symptom severity, global functioning, and ERP. Side effect indicators include common side effect evaluate, extrapyramidal symptoms, metabolic profiles, hormonal change, and bone metabolism indices. Participants will also receive examinations for blood drug concentration, genetic polymorphisms, and epigenetic markers.

NCT02433717 Schizophrenia Schizoaffective Disorder
MeSH:Schizophrenia Psychotic Disorders
HPO:Psychosis Schizophrenia

1 Interventions

Name: Paliperidone ER

Description: Fixed dose (9 mg/day) of paliperidone ER will be given in the first two weeks of trial (from day 1 to day 14). Since the third week (day 15), the dosage can be adjusted in the range of 6 to 12 mg per day.
Type: Drug
Group Labels: 1

Paliperidone ER


Primary Outcomes

Description: Whether the concentration of blood paliperidone is related to the clinical response rate on day 42. Clinical response is defined as achieving 50% or more improvement in terms of PANSS total score: [(PANSS at evaluation - PANSS at baseline)/ (PANSS at baseline - 30)]*100% ≥ 50%

Measure: Pharmacodynamics factor on response rate

Time: day 42

Description: Whether 1236C/T of the ABCB1 gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: ABCB1

Time: day 42

Description: Whether Ser9Gly of the DRD3 gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: DRD3

Time: day 42

Description: Whether Ser311Cys of the DRD2 gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: DRD2

Time: day 42

Description: Whether 267T/C of the 5HTR6 gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: 5HTR6

Time: day 42

Description: Whether 102T/C of the 5HTR2A gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: 5HTR2A

Time: day 42

Description: Whether 995G/A of the 5HTR2C gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: 5HTR2C

Time: day 42

Description: Whether dinucleotide repeat (GT)n of the BDNF gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: BDNF

Time: day 42

Description: Whether val108/158Met of the COMT gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: COMT

Time: day 42

Description: Whether polymorphisms of RGS4 gene is associated with the clinical response rate on day 42.

Measure: Pharmacogenetic factor on response rate: RGS4

Time: day 42

Secondary Outcomes

Description: Measured by Personal and Social Performance Scale (PSP)

Measure: Change in person and social function

Time: day 4, day 7, day14, day 28, and day 42

Description: Measured by Clinical Global Impression-Severity (CGI-S) 2. Side effect variables: DIEPSS, UKU side effect scales, body weight, blood chemistry markers, metabolic markers, hormonal markers, and bone turnover markers

Measure: Change in global impression of the patient

Time: day 4, day 7, day14, day 28, and day 42

Description: Mismatch negativity is an event-related potential measurement

Measure: Change in mismatch negativity

Time: day 42

Description: P50 is an event-related potential measurement

Measure: Change in P50

Time: day 42

Description: Auditory steady state response is an event-related potential measurement

Measure: Change in auditory steady state response

Time: day 42

Description: CPT is a neurocognitive test

Measure: Change in attention as measured by Continuous Performance Test (CPT)

Time: day 42

Description: WCST is a neurocognitive test

Measure: Change in executive function as measured by Wisconsin Card Sorting Test (WCST)

Time: day 42

Description: Trail-A test is a neurocognitive test

Measure: Change in performance on Trail-A test

Time: day 42

Description: Trail-B test is a neurocognitive test

Measure: Change in performance on Trail-B test

Time: day 42

Description: Verbal fluency test is a neurocognitive test

Measure: Change in performance on verbal fluency test

Time: day 42

Description: Digit Span is a subtest of Wechsler Adult Intelligence Test-III

Measure: Change in performance on Digit Span

Time: day 42

Description: Arithmetic is a subtest of Wechsler Adult Intelligence Test-III

Measure: Change in performance on Arithmetic

Time: day 42

Description: Clinical response are defined as 50% or more improvement in terms of PANSS total score: [(PANSS at evaluation - PANSS at baseline)/ (PANSS at baseline - 30)]*100% ≥ 50%

Measure: Pharmacodynamics and pharmacogenetics factors on response rate

Time: day 4, day 7, day14, day 28

Description: Severity of extrapyramidal symptoms is measured by Drug-Induced Extrapyramidal Symptom Scale (DIEPSS)

Measure: Severity of extrapyramidal symptoms

Time: day 4, day 7, day14, day 28, day 42

Description: Severity of side effects is measured by Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale

Measure: Severity of side effects

Time: day 4, day 7, day14, day 28, day 42

Description: AC sugar

Measure: Effects on blood glucose level

Time: day 14 and day 42

Measure: Effects on blood cholesterol level

Time: day 14 and day 42

Measure: Effects on blood triglyceride level

Time: day 14 and day 42

Measure: Effects on blood HDL-cholesterol level

Time: day 14 and day 42

Measure: Effects on blood prolactin level

Time: day 14 and day 42

Measure: Effects on blood leptin level

Time: day 14 and day 42

Measure: Effects on adiponectin level

Time: day 14 and day 42

Measure: Effects on blood alkaline phosphatase level

Time: day 42

Measure: Effects on blood calcium level

Time: day 42

Measure: Effects on blood phosphate level

Time: day 42

Measure: Effects on blood bone-specific alkaline phosphatase level

Time: day 42

Measure: Effects on blood intact osteocalcin level

Time: day 42

Measure: Effects on blood oestradiol level

Time: day 42

Measure: Effects on blood progesterone level

Time: day 42

Measure: Effects on blood LH level

Time: day 42

Measure: Effects on blood FSH level

Time: day 42

Measure: Effects on blood testosterone level

Time: day 42

Measure: Effects on blood uric acid level

Time: day 14 and day 42

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There are 2 SNPs

SNPs


1 S311C

Whether Ser311Cys of the DRD2 gene is associated with the clinical response rate on day 42.. Pharmacogenetic factor on response rate: 5HTR6. --- Ser311Cys ---

Blood sampling on day 0 (40 ml), day 14 (15 ml) and day 42 (40 ml): 1. Blood paliperidone concentration and pharmacodynamics of risperidone and paliperidone on day 0, day 14, and day 42. 2. Blood biochemistry study (AC sugar, uric acid, cholesterol, triglyceride, HDL-cholesterol, leptin, adiponectin, prolactin) on day 0, day 14, and day 42. 3. Bone turnover markers (serum alkaline phosphatase, calcium, phosphate bone-specific alkaline phosphatase, intact osteocalcin), and hormonal markers (oestradiol, progesterone, LH, FSH and testosterone) on day 0 and day 42. 4. DNA sample for genetic markers on day 0: 1236C/T of the ABCB1 gene, Ser9Gly of the DRD3 gene, Ser311Cys of the DRD2 gene, 267T/C of the 5HTR6 gene, 102T/C of the 5HTR2A gene, 995G/A of the 5HTR2C gene, dinucleotide repeat (GT)n of the BDNF gene, val108/158Met of the COMT gene, and polymorphisms of the RGS4 gene. 5. Epigenetic markers on day 0 and day 42. --- Ser9Gly --- --- Ser311Cys ---


2 S9G

Whether Ser9Gly of the DRD3 gene is associated with the clinical response rate on day 42.. Pharmacogenetic factor on response rate: DRD2. --- Ser9Gly ---

Blood sampling on day 0 (40 ml), day 14 (15 ml) and day 42 (40 ml): 1. Blood paliperidone concentration and pharmacodynamics of risperidone and paliperidone on day 0, day 14, and day 42. 2. Blood biochemistry study (AC sugar, uric acid, cholesterol, triglyceride, HDL-cholesterol, leptin, adiponectin, prolactin) on day 0, day 14, and day 42. 3. Bone turnover markers (serum alkaline phosphatase, calcium, phosphate bone-specific alkaline phosphatase, intact osteocalcin), and hormonal markers (oestradiol, progesterone, LH, FSH and testosterone) on day 0 and day 42. 4. DNA sample for genetic markers on day 0: 1236C/T of the ABCB1 gene, Ser9Gly of the DRD3 gene, Ser311Cys of the DRD2 gene, 267T/C of the 5HTR6 gene, 102T/C of the 5HTR2A gene, 995G/A of the 5HTR2C gene, dinucleotide repeat (GT)n of the BDNF gene, val108/158Met of the COMT gene, and polymorphisms of the RGS4 gene. 5. Epigenetic markers on day 0 and day 42. --- Ser9Gly ---



HPO Nodes


HPO: