Effect of Genetic Association With Functional Dyspepsia and Mood Disorders (FDFDR)

Background:

Functional dyspepsia (FD) is one of the commonest digestive disorders. The pathophysiology of functional dyspepsia is uncertain. Risk factors include genetics, gender, age, helicobacter pylori infection, etc. However, few reported the association of genetic contribution to the development of FD and mood disorder.

Indication:

Functional dyspepsia patients

Study center(s):

Prince of Wales Hospital, Hong Kong

Aims:

• To evaluate genetic factors on development of functional dyspepsia & common mood disorders
• To evaluate genetic factors on the severity of function dyspepsia & mood disorders
• To develop a diagnostic test for classification of functional dyspepsia by plasma ghrelin and serotonin expression
• To collect sleep data for future use
• To save blood sample for future retrospective diagnostic or genetic examination

Study design:

Case-control cross sectional study

Number of subjects:

Total of 1200 subjects (300 FD patients + 300 relatives of FD patients FDR) and (300 Controls + 300 FDR)

Patient population:

Functional dyspepsia patients age 18-60

Duration of study:

1 May 2012 - 30 April 2013

Primary variable(s):

Genetic polymorphisms of targeted genes, plasma ghrelin and serotonin expression

Secondary variable(s):

FD global symptom assessment and symptom scores

Number of visits: 1

Hypotheses:

• Shared genetic factors contribute to the development of FD and common psychological disorders
• FD patients contribute to suppression of plasma ghrelin and serotonin expression compared to healthy controls

Study Overview

• Status: Unknown
• Conditions: Dyspepsia

Detailed Description

Methods:

All subjects will participate in (1) Demographic assessment, (2) Questionnaires administration and (3) Blood sample collection. The three steps must be completed within 2 weeks.

1. Demographic assessment

   • Demographic: age, gender
   • Anthropometric measurements: body mass index, height, weight
   • Smoke and drink habit
   • Comorbidity and medical history

2. Questionnaires administration

   • A combined functional gastrointestinal (GI) symptom questionnaire (FGISQ) based on recall of the past 7 days will be used for assessment all GI symptoms including regurgitation, heartburn, epigastric pain, postprandial fullness, abdominal pain, diarrhea, constipation etc. All questions use a 4-point (0-3) Likert scale.
   • FGI Screening Questionnaire (v.3, 20101011) for screening of functional gastrointestinal disorder according to Rome III criteria. The questionnaire incorporate a GERD diagnostic questionnaire GERDQ (Chinese version)
   • Hospital Anxiety and Depression Scale (HADS) for a self administered scale for seven covering depression and seven covering anxiety.
   • Psychological disorder: Patient Health Questionnaire (PHQ) will be used for screening of concomitant psychological disorder such as depression and generalized anxiety disorder.
   • The Epworth Sleepiness Scale, Pittsburgh sleep quality index, and General Sleep Quality Questionnaire to collect sleep data for future use.

3. Blood sample collection

   • Up to 20 ml of fasting blood sample will be collected for study aims 1-4.
   • Fasting glucose test will be performed for FD patients
   • Serology test of Hp status will be performed for healthy volunteers and all FDRs

Subjects who had fasting glucose test or serology test performed within one year before study enrollment can be exempted from repeating the tests if they refuse to repeat the tests. In such cases, their previous test results will be recorded and used in this study.

If the subjects are found to be positive as a result of Helicobacter pylori (Hp) serology test, a referral letter with prescription suggestion will be given to the subjects to seek proper medical care in the primary care setting. In current practice, Hp eradication is not mandatory for asymptomatic subjects.

Laboratory work:

Nine ml of blood will be used for the detection of biomarkers for functional dyspepsia through single nucleotide polymorphism (SNPs). The genotyping DNA will be isolated from whole blood samples by (FlexGene DNA kit, Qiagen). High-throughput genotyping will be performed on the serotonin 3A receptor polymorphism (rs1062613) and ghrelin CLOCK 3111C polymorphism (rs1801260). It will be analyzed by Applied Biosystems (ABI) 3730xl DNA Analyzer.

Six ml of blood will be used for detection of plasma ghrelin and serotonin expression for development of diagnostic test in classification of functional dyspepsia by ELISA.

• Study Type: Observational
• Enrollment (Anticipated): 1200

Contacts and Locations

• Study Contact: Name: Justin C.Y. Wu, MBChB(CUHK); Phone Number: (852)35053476; Email: justinwu@cuhk.edu.hk
• Study Contact Backup: Name: Kay Yuen, M Phil; Phone Number: (852)35053476; Email: kayyuen@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital
    • Principal Investigator: Justin C.Y. Wu, MBChB(CUHK)
    • Contact: Justin C.Y. Wu, MBChB(CUHK); Phone Number: (852)35053476; Email: justinwu@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients referred for OGD in Endoscopy Center, Prince of Wales Hospital, with symptoms suggestive of FGID or who participated in PI's previous clinical trials will be invited to participate in this study as FD patients.

Patients not suffering from FGID will be identified from the gastrointestinal specialty clinic or Endoscopy Center, Prince of Wales Hospital as healthy volunteers. These patients may include those referred for GI malignancy screening.

Study advertisement will be posted in public area of Prince of Wales Hospital, and on the educational website (www.digestion.hk) which is maintained by PI. Controls who are self-referred to this study will be recruited.

Description

Inclusion Criteria:

• All subject

  • Age 18-60
  • Provision of written consent

Additional to FD patient

• Symptoms fulfilling Rome III criteria of functional dyspepsia
• Negative upper endoscopy (oesophagogastroduodenoscopy or OGD) finding

Exclusion Criteria:

• All subject

  • History of cancer
  • Diabetes mellitus
  • History of gastric surgery
  • Acid suppressants or medications that affect motility in past 4 weeks
  • Organic disease as cause of dyspepsia (for subjects with dyspeptic symptom)

Additional to healthy volunteer

• Any gastrointestinal symptoms (including acid regurgitation, heartburn, epigastric pain, bloating sensation, constipation, abdominal pain, diarrhea) in the past 4 weeks

Additional to FD patient

• Frequent (once or more per week) acid reflux or heartburn symptoms
• Helicobacter pylori (Hp) infection

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
•FDR-Relatives of FD patients; Relatives of FD patients. Patients may bring at most two FDRs to participate in this study.; Up to 20 ml of fasting blood sample will be collected; Serology test of Hp status will be performed for healthy volunteers and all FDRs
•FDC-Healthy control; Healthy control. Controls who are self-referred to this study will be recruited.; Up to 20 ml of fasting blood sample will be collected; Fasting glucose test will be performed for FD patients; Serology test of Hp status will be performed for healthy volunteers and all FDRs
•FD-Patients with FD; Patients with FD. Patients referred for OGD in Endoscopy Center, Prince of Wales Hospital, with symptoms suggestive of FGID will be invited to participate in this study.; Up to 20 ml of fasting blood sample will be collected; Fasting glucose test will be performed for FD patients
•FDCR-Relatives of healthy controls; Relatives of healthy controls. Each participating control is required to bring at least one and up to two FDRs to participate in this study.; Up to 20 ml of fasting blood sample will be collected; Serology test of Hp status will be performed for healthy volunteers and all FDRs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of genetic polymorphism in targeted genes in patients with FD and mood disorders	Differences of genetic polymorphism in targeted genes in patients with FD and mood	up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of psychiatric disorder with PHQ and HADS	Diagnosis of psychiatric disorder with PHQ and HADS	up to 48 months
Differences of plasma ghrelin and serotonin expression in FD patients and study controls.	Differences of plasma ghrelin and serotonin expression in FD patients and study controls.	up to 48 months
Symptom scores	Symptom scores	up to 48 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Justin C.Y. Wu, MBChB(CUHK), Chinese University of Hong Kong

Publications and helpful links

Helpful Links

• The Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: April 17, 2014
• First Submitted That Met QC Criteria: November 2, 2014
• First Posted (Estimate): November 5, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: April 23, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Functional dyspepsia; symptom response
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Dyspepsia; Mood Disorders
• Other Study ID Numbers: FDFDR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO