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

NCT ID: NCT01931540

Last Updated: 2016-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2015-06-30

Brief Summary

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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).

Detailed Description

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Conditions

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Maternal-Fetal Relations Muscle Weakness Insulin Resistance

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Exercise Training - 17 offspring of OM

4 months exercise training, OM: Obese mothers

Group Type EXPERIMENTAL

Exercise Training

Intervention Type BEHAVIORAL

Three times a week, for four months.

11 non-frail controls (9 LM)

Studied only at baseline

Group Type NO_INTERVENTION

No interventions assigned to this group

Exercise Training - 20 offspring of LM

4 months exercise training, LM:Lean/Normal Mothers

Group Type EXPERIMENTAL

Exercise Training

Intervention Type BEHAVIORAL

Three times a week, for four months.

Interventions

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Exercise Training

Three times a week, for four months.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University of Turku

OTHER

Sponsor Role collaborator

University of Helsinki

OTHER

Sponsor Role collaborator

Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

OTHER_GOV

Sponsor Role collaborator

Istituto Superiore di Sanità

OTHER

Sponsor Role collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Pirjo Nuutila

MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pirjo Nuutila, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Turku PET Centre (Turku University Hospital)

Locations

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

Helsinki, , Finland

Site Status

Turku PET Centre (Turku University Hospital)

Turku, , Finland

Site Status

Countries

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Finland

References

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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.

Reference Type DERIVED
PMID: 28952131 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27669153 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26486356 (View on PubMed)

Other Identifiers

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EC-FP7-278603

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

T55/2012b

Identifier Type: -

Identifier Source: org_study_id

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