The Platform for Interdisciplinary Cardiovascular-metabolic-neurovascular Diseases (PICMAN) (PICMAN)

The Platform for Interdisciplinary Cardiovascular-metabolic-neurovascular Diseases (PICMAN) Across National University Health System (NUHS)

Background Changes in metabolism and mitochondrial function appear to precede cardiac dysfunction, with much evidence supporting metabolic dysregulation as one of the earliest precursors of cardiovascular disease. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) across National University Health System (NUHS) is a pilot, prospective, multi-ethnic cohort study in Singapore.

Through extensive phenotyping in a preventive cardiology cohort, the central aim is to define the metabolic flexibility range in a cohort of individuals at elevated risk of atherosclerotic cardiovascular disease, to correlate metabolic flexibility to measures of cardiometabolic health, including diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease.

Study Overview

• Status: Recruiting
• Conditions: Cardiometabolic Syndrome

Detailed Description

Aims

1. Define norms for metabolic flexibility in a multi-ethnic Southeast Asian cohort of individuals without manifest ASCVD
2. Understand the association of metabolic inflexibility with cardiovascular measures of diastolic dysfunction and coronary and cerebral atherosclerosis
3. Understand the association of metabolic inflexibility with measures of body fat distribution
4. Understand the correlation between metabolic flexibility and insulin sensitivity along the spectrum of subclinical cardiovascular disease and severity of non-alcoholic fatty liver disease
5. Associations of the gut microbiome as well as metabolomic and molecular markers with cardio-cerebrovascular measures, metabolic flexibility and liver fibrosis

The PICMAN study seeks to lay the foundations for further future larger scale and more experimentally ambitious studies based on the overarching hypothesis that metabolic flexibility is an early marker in subclinical cardiovascular disease, indicating a point of timely intervention where the disease process is still reversible. The importance of a deeply-phenotyped local cohort will allow us to study the progression of CVD in seemingly well adults, converging imaging, biochemical, metabolic markers, and 'omics analysis.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Mayank Dalakoti; Phone Number: +6566011036; Email: mayank_dalakoti@nuhs.edu.sg
• Study Contact Backup: Name: Roger Foo; Phone Number: +6566011036; Email: roger.foo@nus.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Health System
    • Contact: Sankari Ramanathan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants between the ages of 21 and 70 at screening without a prior history of MACE, coronary artery disease diagnosis, established diabetes, with a calculated 10-year ASCVD risk > 5% based on QRISK3 calculator are eligible for PICMAN. Recruitment of individuals takes place at NUHS, where community-dwelling individuals without cardiac disease will be referred via outreach to primary care and community partners in Singapore.

Description

Inclusion Criteria:

• Patients aged 21-70 at screening
• 10-year ASCVD risk > 5% measured by QRISK 3 calculator

Exclusion Criteria:

• Established DM (Prior diagnosis, long term medications or HbA1c >=6.5)
• Established CVD, such as ischemic heart disease, cerebrovascular accident, heart failure, atrial fibrillation
• Pregnancy
• Known contraindications to CT scan, such as allergy to contrast

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic flexibility	Metabolic flexibility will be calculated (deltaRQ)	Up to 5 years

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: Mayank Dalakoti, National University Health System; Principal Investigator: Roger Foo, National University Health System

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome
• Other Study ID Numbers: PICMAN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No