Effects of lifestyle changes in an obese metabolically healthy elderly population

ISRCTN	ISRCTN11769612
DOI	https://doi.org/10.1186/ISRCTN11769612
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	PI18/00766
Sponsor	Instituto de Investigación Biomédica de Málaga
Funder	Instituto de Salud Carlos III

Submission date: 11/11/2021
Registration date: 29/11/2021
Last edited: 20/12/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Metabolically Healthy Obese individuals (MHO) are special, seemingly protected from the cardiometabolic disorders associated with excess body fat. The aim of this study is to test whether the change of lifestyle by promoting physical exercise and recommendations of a healthy Mediterranean-style diet (without caloric restriction) in elderly MHO is associated with changes in insulin sensitivity and metabolomic mechanisms.

Who can participate?
Persons aged over 65 years, with a body mass index of 30-40 kg/m² and one or fewer common health issues associated with obesity.

What does the study involve?
Participants will be encouraged to follow a Mediterranean diet based on the Trichopoulou index and practice regular adapted physical activity for 24 months. During the follow-up, 4 visits are planned: baseline and at 4, 12, and 24 months.

What are the possible benefits and risks of participating?
There are no other potential risks from participating in this study other than discomfort from taking blood samples. The potential benefits derive from following a healthy Mediterranean diet and practicing adapted physical activity, which have been shown to prevent cardiovascular disease.

Where is the study run from?
Regional University Hospital of Malaga (Spain)

When is the study starting and how long is it expected to run for?
July 2018 to March 2022

Who is funding the study?
Institute of Health Carlos III (Spain)

Who is the main contact?
Dr. M Rosa Bernal-Lopez, robelopajiju@yahoo.es.

Contact information

Dr M Rosa Bernal-López
Scientific

Internal Medicine Department
Regional University Hospital of Malaga
Instituto de Investigación Biomédica de Málaga (IBIMA)
Avda. Hospital Civil, s/n.
Malaga
29009
Spain

ORCID ID	0000-0002-0238-0890
Phone	+34 951290346
Email	robelopajiju@yahoo.es

Dr M Rosa Bernal-López
Public

Internal Medicine Department
Regional University Hospital of Malaga
Instituto de Investigación Biomédica de Málaga (IBIMA)
Avda. Hospital Civil, s/n.
Malaga
29009
Spain

Phone	+34 951290346
Email	robelopajiju@yahoo.es

Study information

Primary study design	Interventional
Study design	Interventional cross-sectional open study
Secondary study design	Non randomised study
Participant information sheet	40658_PIS.pdf
Scientific title	Obese metabolically healthy elderly population: -omic studies (epigenetics, metabolomics, metagenomics) and its relationship with environmental pollutants
Study objectives	H1. It is postulated that the maintenance and/or weight loss produced by a change in lifestyle, mediated by changes in dietary habits and physical activity, and undertaken at the community level in the elderly Metabolically Healthy Obesity (MHO), will improve insulin sensitivity, compared to the non-responder group. Environment factors such as diet are able to modify the profile of epigenetic changes and, consequently, influence the development of obesity-associated diseases such as insulin resistance. H2. It is postulated that epigenetic modifications (on histones and in the promoter region) in genes involved in insulin resistance in obesity (epiobesigenes) are responsible for the development of the same, through the regulation of gene expression of genes regulating expansion ability, adipose tissue differentiation, adipogenesis, lipogenesis and inflammation. H3. It is postulated that the components of the microbiota have an immune function, a trophic function and digestive function. For this, interindividual variability exists depending on the composition of the flora, which can modify the energy value of food.
Ethics approval(s)	Approved 26/07/2018, Comité de Ética de la Investigación Provincial de Málaga (Hospital Regional Universitario de Málaga, Avnda. Carlos Haya s/n, Pabellón A, 7º planta, Málaga, Spain; +34 951 29 19 77; gloria.luque.exts@juntadeandalucia.es), ref: PI18/00766-260718
Health condition(s) or problem(s) studied	Lifestyle intervention in metabolically healthy obese older adults
Intervention	Participants will be encouraged to follow a Mediterranean diet advised by a nutritionist based on the Trichopoulou index and practice regular adapted physical activity for 24 months. The recommended caloric intake is 1500-1750 kcal/day, distributed as follows: 30% from fats (5-8% from saturated fatty acids, 15-18% from monounsaturated fatty acids, 5-8% from polyunsaturated fatty acids and <300 mg of cholesterol/day), 55% from carbohydrates (<10% from simple sugars, 40% from complex sugars and low glycemic index) and 15% from protein. The recommended Mediterranean diet is based on the Trichopoulou criteria, prioritizing olive oil as the main cooking fat, consuming poultry or rabbit meat preferably rather than red meat and encouraging the consumption of fish, fruits, legumes and vegetables. Similarly, participants are encouraged to practice daily physical activity adapted to their age and physical condition, following the internationally-accepted physical activity guidelines (Physical Activity Guidelines for Americans. Chapter 5. Available at https://health.gov/our-work/physical-activity/current-guidelines). The intervention will last 24 months. Visits will be made at baseline and then at 4 and 12 months to reinforce the intervention and monitor the study variables and at 24 months to monitor the study variables for the last time. Lipid profile, inflammatory biomarkers (hsPCR, IL6, TNFa, fibrinogen) and adipokines (adiponectin, leptin) will be analyzed. Epigenetic (methylation), metabolomic, and metagenomic (gut microbiota) studies will be carried out and their possible relationship with different environmental pollutants will be analyzed.
Intervention type	Behavioural
Primary outcome measure(s)	The primary outcome is a composite outcome where the researchers will analyze the effectiveness of a multidisciplinary and multicomponent intervention carried out in the community setting, aimed at modifying the lifestyle (use of a Mediterranean diet and promotion of physical activity) to prevent the incidence of cardiometabolic alterations in elderly healthy metabolically obese subjects. This has been quantified as an improvement in Mediterranean diet adherence through food frequency questionnaires (baseline and 4, 12 and 24 months) and improvement in physical activity intensities, measured by accelerometry (minutes/day). 1. Nutritional assessment and monitoring: food intake analyzed using questionnaires at baseline and at 4, 12 and 24 months: 1.1. A non-consecutive, 3-day dietary record (two workdays and one weekend day), containing detailed information about food composition and cooking recipes over 72 hours 1.2. A food frequency questionnaire (number of times/day, number of days/week, number of days/14 days, number of days/month, rarely, or never) 1.3. Adherence to Mediterranean diet assessed by a validated 14-item food consumption frequency questionnaire 2. Physical activity monitored using a GENEActiv Actigraph GT3X+ accelerometer at baseline and at 4, 12 and 24 months. The accelerometer should be worn under the chest with a tight elastic belt to ensure close contact with the body. Recordings are made every day for at least 7 days (weekdays and the weekend) to take their hours of physical activity and sleep, except during water activities. Physical activity is also evaluated using the Rapid Assessment of Physical Activity (RAPA) questionnaire, a validated 7-item questionnaire at baseline and at 4, 12 and 24 months
Key secondary outcome measure(s)	1. Anthropometric variables measured by trained personnel at baseline and at 4, 12 and 24 months: 1.1. Weight measured using an electronic scale: TANITA Body Composition Analyzer. Type TBF-300 MA. (TANITA Corporation; 1-14-2 Maeno-cho, Itabashi-ku. Tokio, Japan) 1.2. Height measured with no shoes using a wall stadiometer (Stadiometer Barys Electra Model. 511-300-A0A. ASIMED) 1.3. BMI calculated by dividing weight (kg) by height squared (m²) 1.4. The waist/hip index (WHI) calculated as the ratio of abdominal circumference (at the level of the mid-point between the anterosuperior iliac crest and the last costal arch, parallel to the ground and upon exhalation) and hip, both in cm 1.5. Blood pressure measured with a validated automated electronic sphygmomanometer (OMRON M7 (HEM-780-E, OMRON Healthcare Co. Ltd, Kyoto, Japan) after 5 minutes of rest while the participant is in a seated position 2. Serum adipokine and inflammatory biomarkers levels (IL-6 and TNFa) measured using an enzyme-linked immunosorbent assay (ELISA) (R&D Systems, Inc., Minneapolis, MN, USA) on blood samples collected after an overnight fast at baseline and at 4, 12 and 24 months 3. High-sensitivity CRP levels measured using ELISA (DRG Instruments GmbH, Germany) on blood samples collected after an overnight fast at baseline and at 4, 12 and 24 months
Completion date	31/03/2022

Eligibility

Participant type(s)	Healthy volunteer
Age group	Senior
Lower age limit	65 Years
Sex	All
Target sample size at registration	150
Total final enrolment	169
Key inclusion criteria	1. Aged >65 years 2. BMI ≥30-<40 kg/m² 3. One or none of the following four cardiometabolic disorders: 3.1 Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg 3.2 Triglycerides ≥150 mg/dl 3.3 HDL-C <40 mg/dl in men and <50mg/dl women 3.4 Fasting blood glucose ≥100 mg/dl, following the WHO criterion of MHO
Key exclusion criteria	1. Diabetes 2. Hypertension 3. Previous cardiovascular disease (coronary, cerebrovascular or peripheral; aortic aneurysm, heart failure) 4. Severe associated disease (advanced organ failure, dementia, cancer) 5. Immobilized or terminally ill individuals 6. Alcoholism or drug addiction 7. Severe psychiatric illness 8. Weight loss ≥5 kg in the last 6 months of unknown cause.
Date of first enrolment	01/11/2018
Date of final enrolment	10/03/2020

Locations

Countries of recruitment

Spain

Study participating centre

Regional University Hospital of Málaga

Avda. Carlos Haya, s/n
Málaga
29007
Spain

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and analysed during the current study are available upon request from María Rosa Bernal-López (robelopajiju@yahoo.es). Data is already partially available and will be stored for the next 10 years. Each participant gave their written consent and data was anonymized by giving each participant an identification number code. Data are available if the study results need to be checked.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/09/2022	10/10/2022	Yes	No
Results article		13/11/2021	10/10/2022	Yes	No
Results article		09/06/2022	10/10/2022	Yes	No
Participant information sheet			15/11/2021	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol (other)		09/06/2022	20/12/2023	No	No

Additional files

40658_PIS.pdf: Participant information sheet

Editorial Notes

20/12/2023: Protocol added.
10/10/2022: Publication references added.
15/11/2021: Trial's existence confirmed by the Comité de Ética de la Investigación Provincial de Málaga.