Clinical trial NCT06092372: The Role of Genetics in Weight Loss
Official title: The Role of Genetics in Weight Loss: a Randomized Diet Intervention Study in Individuals with High or Low Genetic Risk for Obesity (GENEROOS Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Body Mass Index (BMI)
Lead sponsor: University of Helsinki
Sponsor class: OTHER
First posted: 2023-10-23
Enrollment: 238
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The prevalence of both overweight and obesity is increasing at an alarming rate worldwide. In fact, it is estimated that 2.16 billion adults (38%) will be overweight and 1.12 billion adults (20%) will be obese by 2030. Among other risk factors (e.g., environmental, behavioral, and medical), genetics holds an important role. Genome-wide association studies have discovered hundreds of loci associated with body mass index (BMI). Polygenic scores (PS) are generated from a combination of millions of genetic variants that are associated with BMI. Several diet intervention studies aimed at reducing body weight in overweight and obese individuals. However, the effect of genetic background on the effectiveness of diet interventions is largely unknown. To our knowledge, the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial is the only prospective study that has been designed to evaluate the effect of genotypes in modifying the impact of a healthy low-fat diet vs a healthy low-carbohydrate diet on weight change, but this study did not consider PS.

The aim of our study is to determine whether BMI PS impacts the effectiveness of dietary intervention in reducing BMI among individuals with elevated BMI.

To achieve this, the investigators will leverage the unique opportunity provided by the Finnish biobanks research environment to re-contact 1200 individuals who have extreme genetic predisposition for high/low BMI as measured by a PS for BMI and evaluate how a randomized diet intervention effect varies between the two extreme groups. In brief, the investigators will invite overweight (25-35 BMI) individuals with very high (Top 5%; n=600) and very low (Bottom 5%; n=600) PS for BMI. Half of the participants in each group will be subsequently randomized to enroll in a dietary/lifestyle coaching intervention program or the placebo group and not receive any dietary advice or information. All participants will be asked to answer an online questionnaire and provide a fasting blood sample at baseline and at the end of the study.

This well-powered prospective study leverages the unique opportunity to re-contact individuals at the extremes of BMI PS from a large pool of individuals with already available genetic information. This study will determine whether BMI PS can be used to identify overweight and obese individuals who are more likely to succeed in a reduced-energy dietary intervention, which will assist our efforts in curbing the overweight and obesity epidemic.


Eligibility criteria: Inclusion Criteria:

* 30-65 years old
* body mass index (BMI) of 25-35
* participants with genetic data available
* participants with a valid recontacting informed consent to their biobank

Exclusion Criteria:

* diagnosis of type I and II Diabetes Mellitus
* history of bariatric surgery
* diagnosis of schizophrenia and intellectual disability
* diagnosis of dementia and Parkinson's
* diagnosis of visual impairment
* diagnosis of multiple sclerosis
* pregnancy or breastfeeding during enrollment screening

Primary outcomes:
measure: Interaction between the top and bottom 5th percentile of the polygenic score (PS) distribution for body mass index (BMI) distribution and BMI reduction
timeFrame: Six months
Secondary outcomes:
Other outcomes:
Locations:
city: Tampere
country: Finland
facility: Finnish Clinical Biobank Tampere
state: Pirkanmaa
Study officials:
affiliation: University of Helsinki
name: Andrea Ganna
role: PRINCIPAL_INVESTIGATOR
References: