Developmental ORIgins of Healthy and Unhealthy AgeiNg: the Role of Maternal Obesity

NCT01931540 | Completed

• 2 other identifiers: T55/2012bEC-FP7-278603
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

The prevalence of obesity in the developed world has increased markedly over the last 20 years. Considering the prevalence of obese and overweight adult subjects, and the fact that pregnancy itself induces a state of insulin resistance and inflammation, maternal obesity may be the most common health risk for the developing fetus. It is well established that what we eat has a major impact on our health. However, there is growing evidence to suggest that diet during pregnancy and lactation may be particularly important as not only does it influence the health of the mother, it may have a permanent effect on the health of her children and even her grandchildren. The concept that environmental factors, such as nutrition during early development, influence both our health span and lifespan has been termed the developmental origins of health and disease hypothesis. The objective of the study are:

• to compare subjects with frailty (condition developed with ageing) with controls and characterize the unhealthy aged condition with the measurements described below
• to examine if signs of frailty can be reversed by lifestyle induced modifications (exercise training programme) of its primary components (IR, sarcopenia, psychological profile) in offspring of overweight/obese (OOM) vs lean mothers (OLM). The study consists of 37 frail old subjects, age ≥ 65 sub-grouped in 17 OOM, and 20 OLM and 11 non frail controls. These subjects will be studied with positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI) and spectroscopy (MRS) and ultra sounds (US). In addition functional MRI (fMRI) will be performed. Adipose tissue biopsies will be taken. Subjects will undergo characterization of biohumoral markers, a 75 g oral glucose tolerance test, imaging biomarkers (PET/CT, US, fMRI-MRS), genetic biomarkers (DNA and telomere damage) and inflammatory biomarkers (macrophage infiltration) before and after the 4-month lifestyle intervention period (physical exercise). By PET/CT it will be measured tissue-specific IR in skeletal muscle, adipose tissue, liver, myocardium and targeted brain regions. MRS will be used to measure organ steatosis in the skeletal muscle and liver, MRI will be used to measure fat masses in abdominal areas, and fMRI will be performed to assess activation in brain regions regulating cognition and appetite/energy control. US will be used to assess cardiovascular markers (IMT, strain and function).

Conditions

Maternal-Fetal Relations; Muscle Weakness; Insulin Resistance

Keywords

Obesity; Epigenesis, Genetic; Exercise Therapy

Outcome Measures

Primary Outcomes (2)

• Baseline group comparison and Change from Baseline in Insulin-stimulated whole body and organ-specific glucose uptake at 4 months

  Assessed via 18F-Fluorodeoxyglucose (FDG)-PET/CT+Clamp technique

  At day 1 and after 4 months of intervention (for the 15 controls only at baseline)

• Baseline group comparison and Change from Baseline in Epigenetic characterization of DNA samples (Telomere length, H2A.X phosphorilation, mtDNA deletion, p66) at 4 months

  Telomere length, H2A.X phosphorilation, mtDNA deletion are measurements performed in Pisa, National Research Council p66 presence is measured in Rome, Istituto Superiore di Sanita'

  At day 1 and after 4 months of intervention (for the 15 controls only at baseline)

Secondary Outcomes (2)

• Baseline group comparison and Change from Baseline in Fat masses and content via MRI and MRS at 4 months

  At day 1 and after 4 months of intervention (for the 15 controls only at baseline)

• Baseline group comparison and Change from Baseline in MRI brain anatomy and fMRI characterization of activation response to food stimuli of different brain regions at 4 months

  At day 1 and after 4 months of intervention

Study Arms (3)

Exercise Training - 17 offspring of OM

EXPERIMENTAL

4 months exercise training, OM: Obese mothers

Behavioral: Exercise Training

11 non-frail controls (9 LM)

NO INTERVENTION

Studied only at baseline

Exercise Training - 20 offspring of LM

EXPERIMENTAL

4 months exercise training, LM:Lean/Normal Mothers

Behavioral: Exercise Training

Interventions

Exercise Training BEHAVIORAL

Three times a week, for four months.

Exercise Training - 17 offspring of OM; Exercise Training - 20 offspring of LM

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be already participating the Helsinki Birth Cohort Study
• (Frailty) with lowest half of adult grip strength (measured 2001-2004)
• Group OM: (Offspring of Obese mothers) Highest quartile of maternal BMI
• Group LM: (Offspring of Normal weight/Lean mothers) Lowest two quartiles of maternal BMI
• (no Frailty) with highest half of adult grip strength (measured 2001-2004)
• Offspring of normal weight mothers

You may not qualify if:

• Subjects whose mothers were pre-eclamptic during pregnancy
• Oral corticosteroid or Warfarin therapy
• Recent myocardial infarction
• Severe chronic disorder that can prevent to participate the intervention
• Chronic atrial fibrillation and pacemaker
• Cancer less than 5 years ago
• Current smoking
• Diabetes requiring insulin treatment or fasting glucose more than 7 mmol/l
• Weight more than 170 kg and Waist circumference \> 150 cm
• Inner ear implants
• Metal objects in body including metallic prostheses, artificial valve prostheses, surgical clips, braces, foreign fragments or tattoo

Sponsors & Collaborators

• Turku University Hospital: lead
• University of Turku: collaborator
• University of Helsinki: collaborator
• Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy: collaborator
• Istituto Superiore di Sanità: collaborator

Study Sites (2)

University of Helsinki, Department of General Practice and Primary Health Care

Helsinki, 00014, Finland

Location

Turku PET Centre (Turku University Hospital)

Turku, 20521, Finland

Location

Related Publications (3)

• Berry A, Bucci M, Raggi C, Eriksson JG, Guzzardi MA, Nuutila P, Huovinen V, Iozzo P, Cirulli F. Dynamic changes in p66Shc mRNA expression in peripheral blood mononuclear cells following resistance training intervention in old frail women born to obese mothers: a pilot study. Aging Clin Exp Res. 2018 Jul;30(7):871-876. doi: 10.1007/s40520-017-0834-4. Epub 2017 Sep 26.

  PMID: 28952131 DERIVED

• Huovinen V, Bucci M, Lipponen H, Kiviranta R, Sandboge S, Raiko J, Koskinen S, Koskensalo K, Eriksson JG, Parkkola R, Iozzo P, Nuutila P. Femoral Bone Marrow Insulin Sensitivity Is Increased by Resistance Training in Elderly Female Offspring of Overweight and Obese Mothers. PLoS One. 2016 Sep 26;11(9):e0163723. doi: 10.1371/journal.pone.0163723. eCollection 2016.

  PMID: 27669153 DERIVED

• Bucci M, Huovinen V, Guzzardi MA, Koskinen S, Raiko JR, Lipponen H, Ahsan S, Badeau RM, Honka MJ, Koffert J, Savisto N, Salonen MK, Andersson J, Kullberg J, Sandboge S, Iozzo P, Eriksson JG, Nuutila P. Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers. Diabetologia. 2016 Jan;59(1):77-86. doi: 10.1007/s00125-015-3780-8.

  PMID: 26486356 DERIVED

MeSH Terms

Conditions

Muscle Weakness; Insulin Resistance; Obesity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Pirjo Nuutila, MD PhD

  Turku PET Centre (Turku University Hospital)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: April 22, 2013
• First Posted: August 29, 2013
• Study Start: June 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: June 1, 2015
• Last Updated: March 22, 2016

Record last verified: 2016-03

Locations

FI (2)