Clinical trial NCT04714723: Lifestyle Intervention Trial in High Metabolic Risk Chinese
Official title: Lifestyle Intervention Trial in High Metabolic Risk Chinese
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Obesity
Keywords: weight loss,metabolic risk, lifestyle intervention, homeostasis
Lead sponsor: Chinese Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Sir Run Run Shaw Hospital
First posted: 2021-01-19
Enrollment: 395
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In this single-blind, randomized trial, 395 eligible volunteers, who have higher metabolic syndrome (MetS) risk and aged 20-65 years, will be assigned to one of two smartphone-based lifestyle intervention arms: 1) Programmed-smartphone intervention or 2) Programmed-smartphone plus dietitian intervention. Before and after 6-month intervention, "PhenFlex test" (PFT) was performed to examine and quantify improved metabolic flexibility.

This intervention trial will be conducted by researchers in Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences (CAS) collaborating with Zhejiang University affiliated Sir Run Run Shaw Hospital. The study protocol was approved by the Ethics Committees in Shanghai Institutes of Nutrition and Health, and in Sir Run Run Shaw Hospital.

The main aims of this study are to determine 1) efficacy of lifestyle interventions with different intensity in reducing MetS and its risk factors; 2) improved metabolic responses or flexibility defined by PFT-based homeostasis index; and 3) major genetic and nongenetic determinants for the efficacy of interventions among high MetS risk Chinese.

Detailed description: Metabolic syndrome, a cluster of multiple metabolic disturbances, including central obesity, dyslipidemia, hypertension, and hyperglycemia, is associated with 2-5-fold heightened risks of CVD and T2D. Compelling evidence showed that lifestyle intervention is one of effective approaches for preventing and controlling cardiometabolic diseases. However, there were considerably variations among different interventions and different persons. With widely available smartphone and APP-connected wearable devises, it is possible to provide programmed nutrition and lifestyle education to help participants achieve intervention targets, and closely monitor compliance. However, few studies investigated the efficacy of lifestyle interventions with programmed smartphone and APP-connected wearable devises in MetS management. Moreover, since present disease-based diagnoses and biomarkers may not adequately define health status, the concept of "re-redefining health" has attracted growing attention. The phenotypic flexibility and "PhenFlex test" are one of approaches to measure individuals' adaptive capacity to maintain hemostatic condition after having a standardized challenge drinker. To date, the PFT has been studied among 10,000 subjects in western countries and few studies, if any, have conducted in Chinese who have different genetic background and dietary patterns. It remains to be established whether and to what extent that the PFT-based hemostatic index system can precisely evaluate the metabolic health in Chinese.

In the current trial, 395 subjects with MetS risks were randomly assigned to either smartphone-based lifestyle intervention arms: 1) Programmed-smartphone intervention; or 2) Programmed-smartphone plus dietitian intervention. The intervention duration will be 6-month and then have 2-year follow-up. During starting and end of 6-month intervention, we included PFT during the physical examination hold in the Sir Run Run Shaw Hospital. All the subjects were given a standardized challenge drinker (75g glucose, 60 fat and 20g protein). Fasting and multiple postprandial time points samples (blood, t=0,1,3h) and urine and feces were collected to measure clinical and omics markers like metabolomics, gut microbiota and SNPs. Finally, the homeostasis index will be built to estimate improvement of individual metabolic health after the intervention. In conclusion, this study will provide scientific evidence and novel insights about the effectiveness of new intervention strategies and precise diagnostic and assessment system for cardiometabolic management.

Eligibility criteria: Inclusion Criteria:

Volunteers at high metabolic risk aged 20-65 who didn't participate in other studies in 3 months before the current research, having a certain level of education and normal cognitive ability, taking good care of himself/herself. MetS risk factors were identified by the definition proposed by the International Diabetes Federation criteria for Chinese adults. Participants should have central obesity (waist circumference ≥90 cm in men or ≥80 cm in women).

Exclusion Criteria:

* Fasting glucose\>7.0mmol/L after taking insulin or other blood glucose-lowering drugs
* Diagnosed phase three hypertension or can't lowering SBP under 160mmHg after anti-hypertension drugs
* Fasting blood TG≥ 5.7 mmol/L or fasting LDL-C≥ 4.9 mmol/L after taking lipid-lowering drugs
* Pregnancy or lactation
* Obvious drug changing in three months before research
* History of drug or alcohol abuse or other substance abuse (Alcohol abuse is defined as more than 40 g/day of alcohol for woman, and more than 80g/day for man)
* Severe kidney and liver diseases (blood biomarkers such as alt, serum creatinine is 1.5 times over the scope of normal setting)
* Severe Gastrointestinal diseases (such as severe diarrhea, constipation, severe digestive tract inflammation, active peptic ulcer, acute cholecystitis, etc.)
* Having surgeries within one year before research such as heart stents implanted surgery (expect for appendicitis or hernia operation)
* Severe cardiovascular disease (e.g., heart failure, myocardial infarction, cerebral infarction, and acute myocarditis, severe arrhythmia, received the intervention therapy, etc.)
* Cancer or receiving radiotherapy and chemotherapy within 5 years
* Severe pituitary or thyroid diseases
* Suffering from AIDS, hepatitis A, hepatitis B and other infectious diseases
* Mental disorders or current use of antidepressants

Primary outcomes:
measure: Weight
timeFrame: Baseline and month 6
Secondary outcomes:
measure: Body mass index (BMI)
timeFrame: Baseline and month 6
measure: Waist circumference
timeFrame: Baseline and month 6
measure: Blood pressure
timeFrame: Baseline and month 6
measure: Triglyceride
timeFrame: Baseline and month 6
measure: Total cholesterol
timeFrame: Baseline and month 6
measure: LDL-C
timeFrame: Baseline and month 6
measure: HDL-C
timeFrame: Baseline and month 6
measure: Glucose
timeFrame: Baseline and month 6
measure: Metabolic Homeostasis Score
timeFrame: Baseline and month 6
measure: Body composition
timeFrame: Baseline and month 6
measure: Compliance
timeFrame: Whole 6-month intervention
Other outcomes:
measure: E-selectin concentration
timeFrame: Baseline and month 6
measure: P-selectin concentration
timeFrame: Baseline and month 6
measure: Vascular cell adhesion molecule-1(VCAM-1) concentration
timeFrame: Baseline and month 6
measure: Intercellular adhesion molecule-1 (ICAM-1) concentration
timeFrame: Baseline and month 6
measure: Amyloid A1(SAA1) concentration
timeFrame: Baseline and month 6
measure: Tumor Necrosis Factor-α (TNF-α) concentration
timeFrame: Baseline and month 6
measure: Interleukin-10(IL-10) concentration
timeFrame: Baseline and month 6
measure: Interleukin-1b(IL-1b) concentration
timeFrame: Baseline and month 6
measure: C-reactive protein(CRP) concentration
timeFrame: Baseline and month 6
measure: Retinol binding protein(RBP4) concentration
timeFrame: Baseline and month 6
measure: Adiponectin concentration
timeFrame: Baseline and month 6
measure: Metabolomics including profiling of free fatty acids and other metabolites
timeFrame: Baseline and month 6
measure: Single nucleotide polymorphism (SNPs)
timeFrame: Baseline
measure: Gut microbiota 16S rDNA sequencing
timeFrame: Baseline and month 6
measure: HbA1c
timeFrame: Baseline and month 6
measure: Insulin
timeFrame: Baseline and month 6
measure: Glucagon
timeFrame: Baseline and month 6
measure: Glucagon-like peptide-1
timeFrame: Baseline and month 6
measure: Aspartate transaminase
timeFrame: Baseline and month 6
measure: Gastric inhibitory peptide
timeFrame: Baseline and month 6
measure: Alanine aminotransferase
timeFrame: Baseline and month 6
measure: Serum creatinine
timeFrame: Baseline and month 6
measure: γ-glutamyl transpeptidase
timeFrame: Baseline and month 6
measure: Urine creatinine
timeFrame: Baseline and month 6
measure: Urea nitrogen
timeFrame: Baseline and month 6
measure: Uric acid
timeFrame: Baseline and month 6
Locations:
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital;Hangzhou Dianzi University;China Jiliang University; Zhejiang Sci-Tech University
state: Zhejiang
Study officials:
affiliation: Shanghai Institute of Nutrition and Health, Chinese Acadamy of Sciences
name: Xu Lin, PhD
role: PRINCIPAL_INVESTIGATOR
References: