Clinical trial NCT05621109: PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - Copenhagen
Official title: PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - a Randomized Controlled Study in Copenhagen
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Overweight and Obesity
Weight Loss
Pregnancy Related
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Dept. of Obstetrics and Gynecology, Hvidovre Hospital, Denmark
name: Department of Growth and Reproduction Rigshospitalet, Denmark
name: Center for Healthy Childhood, Denmark
name: University of Copenhagen
First posted: 2022-11-17
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study is a single site parallel randomized controlled study.

The study will be assessing the effect of approximately 10% weight loss intervention vs a control group among healthy females/couples where the prospective mother is overweight or obese (BMI 27-45 kg/m\^2) and between 18-38 years. The investigators will recruit a total of 240 healthy females/couples who will be randomized 1:1 to either intervention or control, stratified according to maternal pre-pregnancy BMI.

The overall objective is to test whether a comprehensive pre-conceptional parental weight loss intervention effectively reduces the risk of offspring overweight and adiposity and its complications compared to a control group. The investigators hypothesize that parental weight loss intervention, initiated before conception, will facilitate lower parental insulin resistance, inflammation, body weight and adiposity, incretin responses compared to usual care. For the offspring the investigators hypothesize that the intervention will reduce adverse pregnancy outcomes with a reduction in offspring neonatal adiposity, reduced risk of being born large for gestational age (LGA) and with lower BMI z-score at 18 months.


Eligibility criteria: Maternal inclusion Criteria:

* Maternal pre-pregnancy BMI 27.0-44.9 kg/m\^2
* Maternal age range 18-38 years
* Connected to Hvidovre Hospital as place of birth or willing to change from other Hospitals in Region H to Hvidovre Hospital
* Not pregnant or breastfeeding

Paternal Inclusion Criteria - full protocol (optional participation):

* Paternal pre-pregnancy BMI 18.5-44.9 kg/m\^2
* Paternal age range 18-55 years
* Biological father

Parental Inclusion Criteria:

* Planning pregnancy within 1 year
* Provided voluntary informed consent
* Danish or English speaking
* Intention to permit the planned offspring to participate in the follow-up study
* Able to store biological samples from the offspring at home in the freezer in a box given by the study personnel

Parental Exclusion Criteria:

* Diabetes mellitus (Type 1 or 2)
* Previous or present eating disorder
* Allergy towards ingredients in the very low calorie diet products
* Severe heart, liver or kidney disease
* Conception by in vitro fertilization (intrauterine insemination allowed)
* ≥4 consecutive spontaneous pregnancy loss (female)
* Having tried to conceive or prior time to pregnancy of more than 12 months
* Any medical condition or concomitant medication as judged by the medical responsible
* Adherence to vegan diets or other diets interfering with the dietary guidelines in the study
* Participation in other clinical trial
* Engagement in elite sports or similar strenuous exercise ≥5 h/week
* Blood donation or transfusion within the past month before baseline
* Blood donation during the study
* Inability or unwillingness to follow the study protocol and instructions given by the study personnel
* Pregnancy registered between baseline visit and 4 weeks after the baseline visit (urinary analysis with dipstick)

A detailed description of the exclusion criteria is given below:

Medical conditions as known by the participant:

* Diabetes mellitus (type 1 and 2)
* History or diagnosis of eating disorder (e.g. restrained eating, disinhibition, emotional eating)
* Any significant medical condition as assessed by the investigator (e.g. dysregulated thyroid disease or reproductive diseases)
* Any significant psychiatric disorder (i.e. schizophrenia, bipolar disease or depression) as assessed by the investigator
* Severe chronic heart, liver and kidney disease
* Polycystic ovary syndrome with irregular cycle
* Amenorrhea
* Severely reduced semen quality incl. azoospermia

Medication:

- Current use of medication or use within the previous three months with a potential to affect body weight or pregnancy as judged by the investigator (e.g. systemic corticoids)

Personal/other:

* Having tried to conceive or prior time to pregnancy of more than 12 months
* Weight changes ± 5% three months prior to inclusion
* Severe food allergies, food intolerances or dislike expected to interfere with the study, including allergy towards ingredients in the VLCD products
* Engagement in elite sports or similar strenuous exercise ≥5 h/week
* Blood donation or transfusion within the past month before baseline
* Planned blood donation for other purpose than this study during participation
* Alcohol abuse, as judged by the investigator, within the previous 12 months
* Drug abuse, as judged by the investigator, within the previous 12 months
* Psychological or behavioral problems which, in the judgement of the investigator, would lead to difficulty in complying with the study protocol
* Participation in other clinical trials within the past three months or intention to do so during the study, which are judged by the investigator to affect the present study
* Unable to consume the interventional product for religious reasons, swallowing disorders, other physiological reasons or any other reasons for not being able to follow the recommended diet
* Inability or unwillingness to give written informed consent or communicate with study personnel
* Inability or unwillingness to follow the study protocol and instructions given by the study personnel
* Illiteracy or inadequate understanding of Danish or English language.
* Any other condition that judged by the investigator may interfere with the adherence to the study protocol

Primary outcomes:
measure: Neonatal fat mass
timeFrame: Assessed at birth (strived <24 hours, but allow <48 hours)
Secondary outcomes:
measure: Obstetrics outcome - length of gestational age
timeFrame: Assessed at birth of offspring.
measure: Obstetric - medication use
timeFrame: Collected from initiation of labor until completed birth of offspring.
measure: Obstetric - delivery mode
timeFrame: Collected at birth of offspring.
measure: Obstetric - pregnancy complications
timeFrame: Collected at registration of pregnancy, in gestational age (GA) 8, GA13, GA20, GA28, GA36 and GA39).
measure: Obstetric - Neonatal unit admissions
timeFrame: Collected at birth and until 6 months after birth of offspring.
measure: Obstetric - obstetrics complications
timeFrame: Collected at birth of offspring
measure: Obstetrics - birth defects/abnormalities
timeFrame: Collected at birth of offspring
measure: Neonatal morbidities
timeFrame: Collected at birth of offspring
measure: Fetal and offspring growth - body weight
timeFrame: Collected in gestational age (GA)11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
measure: Fetal and offspring growth - length
timeFrame: Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
measure: Fetal and offspring growth - abdominal circumference
timeFrame: Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
measure: Fetal and offspring growth - crown circumference
timeFrame: Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
measure: Fetal and offspring growth - femur length
timeFrame: Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
measure: Fetal growth - fractional limb volume
timeFrame: Collected in gestational age 28.
measure: Offspring growth - BMI z-score
timeFrame: Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
measure: Offspring growth - weight for gestational age
timeFrame: Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
measure: Offspring growth - large for gestational age
timeFrame: Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
measure: Offspring growth - small for gestational age
timeFrame: Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
measure: Offspring growth - apgar score
timeFrame: Collected at birth of offspring
measure: Offspring growth
timeFrame: Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
measure: Offspring growth - body composition by the POD system
timeFrame: Collected at birth (strived <24 hours, but allow <48 hours), 3, 6, 12 and 18 months after birth of offspring.
measure: Offspring growth - body composition by DEXA scan
timeFrame: Collected at 6, 12 and 18 months after birth of offspring.
measure: Offspring growth - bone markers by DEXA scan
timeFrame: Collected at 6, 12 and 18 months after birth of offspring.
measure: Offspring blood pressure
timeFrame: Collected 6, 12 and 18-months after birth of offspring
measure: Offspring heart rate
timeFrame: Collected 6, 12 and 18-months after birth of offspring
measure: Offspring growth - self-reported body weight
timeFrame: 18 months after birth the study staff will make an annual follow-up phone call to the parents to collect information about the offspring's self-reported body weight until the offspring is 14 of age.
measure: Offspring growth - self-reported height
timeFrame: 18 months after birth the study staff will make an annual follow-up phone call to the parents to collect information about the offspring's self-reported body weight until the offspring is 14 of age.
measure: Adult weight
timeFrame: The intervention: each visit(V) throughout the study (baseline to 18mo. after birth). The control: before pregnancy (baseline, V11 and V14), all visits during pregnancy, at birth, at V27≤6days after birth and 3,6,12 and 18mo. after birth
measure: Adult self-reported body weight (control group)
timeFrame: From baseline to registration of pregnancy (4, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 52 weeks after baseline)
measure: Adult Height
timeFrame: Collected at baseline (V0).
measure: Adult BMI
timeFrame: Collected baseline, visit (V)1-19, registration of pregnancy, in gestational age (GA)8, GA13, GA20, GA28, GA36, GA39, when giving birth and at 3, 6, 12 and 18 months after birth.
measure: Adult anthropometric
timeFrame: Collected prior to pregnancy (at baseline, visit(V)5, V6, V7, V8, V12, and V16 (V5-V16 only the intervention)), during pregnancy (at registration of pregnancy, in gestational age(GA)13 and GA36), and at 3, 6, 12, and 18 months after birth of offspring.
measure: Adult body composition by DEXA scan
timeFrame: Collected at baseline (visit (V)0), at registration of pregnancy (only male) and after birth (≤6 days after birth of offspring). Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult bone markers by DEXA scan
timeFrame: Collected at baseline (visit (V)0), at registration of pregnancy (only male) and after birth (≤6 days after birth of offspring). Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult blood pressure
timeFrame: Collected at baseline (visit (V)0) and in gestational age (GA)36. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult heart rate
timeFrame: Collected at baseline (visit (V)0) and in gestational age (GA)36. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult resting metabolic rate
timeFrame: Collected at baseline visit (V)0. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult resting respiratory quotient
timeFrame: Collected at baseline visit (V)0. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult medication use
timeFrame: Use of medication will be collected at all visits.
measure: Offspring medication use
timeFrame: Birth, after 3, 6, 12, and 18 months after birth of offspring.
measure: Adult reproduction - Time to pregnancy
timeFrame: Registration of pregnancy
measure: Adult reproduction - Success rate
timeFrame: Registration of pregnancy
measure: Reproduction (male) - Sperm motility
timeFrame: Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Reproduction (male) - Sperm concentration
timeFrame: Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Reproduction (male) - Sperm morphology
timeFrame: Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Reproduction (male) - Sperm acrosomal status
timeFrame: Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Reproduction (male) - Sperm DNA fragmentation
timeFrame: Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult glucose metabolism (OGTT, only female)
timeFrame: Collected at gestational age (GA)20 and 28 or only 28 (only female)
measure: Adult glucose metabolism (CGM, only female)
timeFrame: Collected at gestational age (GA)28+GA29
measure: Adult glucose metabolism
timeFrame: Collected at baseline (visit(V)0) and during pregnancy in gestational age (GA)36 (only female). Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult lipid profile
timeFrame: Collected at baseline (visit(V)0) and during pregnancy in gestational age (GA)36 (only female). Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult inflammation markers
timeFrame: Collected at baseline (visit(V)0) and during pregnancy in gestational age (GA)36 (only female). Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Offspring glucose metabolism
timeFrame: Collected at 6, 12 and 18 months after birth
measure: Offspring lipid profile
timeFrame: Collected at 6, 12 and 18 months after birth
measure: Offspring inflammation markers
timeFrame: Collected at 6, 12 and 18 months after birth
measure: Offspring growth factors and hormones
timeFrame: Collected at 6, 12 and 18 months after birth
Other outcomes:
measure: Cord blood - epigenetics
timeFrame: Collected at birth
measure: Cord blood - pH
timeFrame: Collected at birth
measure: Cord tissue
timeFrame: Collected at birth
measure: Placenta
timeFrame: Collected at birth
measure: Placenta - biopsies
timeFrame: Collected at birth
measure: Vaginal swab (female) - Microbiome
timeFrame: Collected at baseline, at gestional age(GA) 13 and GA36. Additionally, the intervention group will collect a sample at visit (V)8 during the intervention period.
measure: Vaginal swab (female) - pH
timeFrame: Collected at baseline, at gestional age(GA) 13 and GA36. Additionally, the intervention group will collect a sample at visit (V)8 during the intervention period.
measure: Offspring feces - Microbiom
timeFrame: Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
measure: Offspring feces - Short chain fatty acids
timeFrame: Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
measure: Offspring feces - Metabolomics
timeFrame: Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
measure: Offspring feces - Proteomics
timeFrame: Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
measure: Offspring feces - pH
timeFrame: Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
measure: Offspring feces - Inflammation markers
timeFrame: Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
measure: Offspring feces - consistency and frequency
timeFrame: Collected at birth (the 4 the day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
measure: Offspring urine
timeFrame: Collected at birth and at 1, 3, 6, 12 and 18 months of age.
measure: Adult feces - Microbiome
timeFrame: Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult feces - Short chain fatty acids
timeFrame: Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult feces - Metabolomics
timeFrame: Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult feces - Proteomics
timeFrame: Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult feces - Inflammation markers
timeFrame: Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult feces - pH
timeFrame: Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult feces - consistency and frequency
timeFrame: Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult urine
timeFrame: Collected at baseline (visitV)0), during pregnancy (GA36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult dietary intake
timeFrame: Collected at baseline (visit(V)0), during pregnancy (GA13 and GA36) and 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Offspring dietary intake
timeFrame: Collected at birth, after 3, 6, 12 and 18 months after offspring birth.
measure: Semen epigenetics marks
timeFrame: Collected at baseline (visit(V)0) and at V11. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Cognitive development of offspring
timeFrame: Collected at 6, 12 and 18 months after birth.
measure: Offspring development
timeFrame: 3, 6, 12 and 18 months after offspring birth.
measure: Offspring language development
timeFrame: Collected 12 and 18 months after offspring birth.
measure: Epigenetics
timeFrame: Collected at baseline (visit(V)0) and at V8 (only intervention group) and in gestational age (GA)36 - only female). Collected at birth for offspring.
measure: Adult physical activity
timeFrame: Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 (only females during pregnancy). Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult physical activity
timeFrame: Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult background
timeFrame: Collected prior baseline V0
measure: Adult wellbeing - Depression
timeFrame: Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult wellbeing - Quality of life
timeFrame: Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult wellbeing - Stress
timeFrame: Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult sleep
timeFrame: Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adult sexual score
timeFrame: Collected at baseline (visit(V)0). Additionally, at V8 (prior to pregnancy) for the intervention group.
measure: Adults liver steatosis and stiffness by Liver ultrasound elastography (FibroScan)
timeFrame: Collected at baseline (Visit(v)0), prior to pregnancy for the intervention group (v8), week 52 in the pre-pregnancy period if pregnancy is not achieved (v19), at gestational age (GA)20 (v23), and 3 months after birth of offspring (v28).
measure: Offspring liver steatosis and stiffness by Liver ultrasound elastography (FibroScan)
timeFrame: Measured at 3 and 18 months after offspring birth.
measure: Breast milk from mother - establishment of lactation
timeFrame: Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
measure: Breast milk from mother - establishment of lactation - inflammatory markers
timeFrame: Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
measure: Breast milk from mother - establishment of lactation - immune markers
timeFrame: Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
measure: Breast milk from mother - establishment of lactation - growth factors
timeFrame: Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
measure: Breast milk from mother - establishment of lactation - appetite regulation hormones
timeFrame: Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
measure: Breast milk from mother - establishment of lactation - microbiome
timeFrame: Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
Locations:
city: Frederiksberg
country: Denmark
facility: University of Copenhagen
state: DK
Study officials:
affiliation: University of Copenhagen
name: Christian Mølgaard, MD
role: PRINCIPAL_INVESTIGATOR
References: