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NCT Number: NCT07065643

Sex Hormones as Regulators of the Age- and Sex-dependent Benefits of Caloric Restriction

Obesity increases the risk of type 2 diabetes, cardiovascular disease, and certain cancers, primarily due to elevated abdominal fat storage. With nearly two-thirds of the UK population living with overweight or obesity, there is an urgent necessity for evidence-based public health guidance to promote healthy weight. Calorie deficit can facilitate weight loss and body fat reduction, leading to health benefits, such as improved blood glucose control. Current weight management advice centres on lifestyle modification, incorporating changes to diet and physical activity to support a calorie deficit. However, existing dieting recommendations fail to consider gender or age. This is a surprising oversight, as it is well established that health outcomes vary significantly between men and women across the lifespan. Further, the menopause may have an impact on fat storage linked to changes in sex hormones. Our recent research, involving both mice and humans, has indicated that females are less responsive to weight loss and fat reduction during dieting. This study aims to understand endocrine and metabolic sex-based differences in obesity and calorie restriction, with a particular focus on women's health. We plan to conduct a diet study with 75 participants, encompassing both younger and older men and women, to monitor changes in energy expenditure and body composition using gold-standard techniques, such as doubly-labelled water. Blood and abdominal fat tissue samples will be collected to investigate how sex hormones might elucidate these differences. The aim of the study is to enhance our understanding of diet and women's health to combat obesity and promote healthy ageing.

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Key information

Conditions

Overweight and Obese Adults Body Weight Healthy Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults (aged over 18years) who are healthy but overweight/obese (BMI 27-45kg/m2) males and females as:
  • 15 women (age 40 or less years)
  • 15 men (age 40 or less years)
  • 15 women (age 55-65 years) in menopause*; not taking Hormone Replacement Therapy (HRT)
  • 15 men (age 55-65 years)
  • 15 women (age 55-65 years) in menopause; taking HRT**
  • menopause definition is no menstrual period for 12 months **HRT inclusion criteria - women will have continuously taken oestrogen HRT for 24 months

Exclusion criteria

Potential volunteers will be asked to fill in a health questionnaire at the screening visit to assess their suitability for the study. This information will allow us to exclude participants.

Medication exclusion criteria, current use :-

  • weight loss medication (e.g. GLP agonists), β-blockers, antihistamines, antipsychotics, benzodiazepines, barbiturates, melatonin, Ritalin, modafinil, soporifics, hypnotics, antiepileptic drugs, diabetes medication (e.g. metformin or insulin).

Self-reported medical exclusion criteria:

  • Females who are planning to be pregnant, are pregnant or are breastfeeding
  • Anyone with coeliac disease or gluten intolerance or food allergy
  • Anyone with diagnosed T1 or T2 diabetes
  • Anyone suffering from a psychiatric disorder or any type of substance abuse

Other exclusion criteria

  • Anyone following a vegetarian or vegan diet
  • Anyone currently following a weight loss programme (that may be affecting lifestyle, physical activity & diet) or undergone gastric band/reduction surgery; including GLP agonist (e.g. Semaglutide injection, Ozempic®).
  • Anyone currently participating in another research study
  • Anyone with unsuitable veins for blood sampling
  • Anyone who is unable to fluently speak, read and understand English
  • Anyone who is unable to comply to an alcohol-free diet for 6 weeks
  • Anyone unable to give fully informed consent

Treatment and study plan

Phase 1 - Maintenance Diet

Other

3d maintenance diet (MT, fixed macronutrient composition of 15% protein, 30% fat and 55% CHO), fed to energy requirements (1.3 X RMR)

Phase 2 - Weight loss diet

Other

6 week calorie restricted high protein diet (CR, fixed macronutrient composition as 30% protein, 35% fat and 35% CHO) fed to energy requirements [0.8 X Resting Metabolic Rate (RMR)], with stepwise reduction of 100kcal/d at week 3 and 5

Primary outcomes

  1. Change in body mass expressed as weight in kilograms (kg)

    Time frame: From baseline (day 1) to end of intervention (day 53); additional measurements taken three times a week throughout the intervention duration

    Measured using digital scale

  2. Change in energy expenditure expressed in kilocalories per day (kcal/day)

    Time frame: From day 11 (start of the calorie-restricted diet) to the end of the intervention (day 52); with additional doses consumed on day 25 and 39

    Measured using stable isotope method - doubly labelled water (DLW) - with urine sample collection

Secondary outcomes

  1. Change in resting metabolic rate (RMR) expressed in kcal/day

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Measured using ventilated hood indirect calorimetry

  2. Change in bone mineral content in grams (g)

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Measured using Dual Energy X-Ray Absorptiometry (DXA) scan

  3. Change in total body water (TBW) in litres (l)

    Time frame: From day 11 (start of the calorie-restricted diet) to end of the intervention (day 53)

    Measured using deuterium dilution, with urine sample collection

  4. Change in total body density expressed in litres (l)

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Measured using BodPod air displacement plethysmography

  5. Change in body fat-mass percentage (%)

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Derived from Lohman's 4-compartment model (body mass; body density; total body water; and bone mineral content)

  6. Change in non-esterified fatty acids (NEFA) concentration in fasted blood sample

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie-restricted diet (day 32)

    Analysed by KONE

  7. Change in concentration of caloric-restriction (CR) related hormones in fasted blood sample

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie restricted diet (day 32)

    Includes: leptin, adiponectin, cortisol; analysed by ELISA

  8. Change in sex hormones concentration in fasted blood sample

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie restricted diet (day 32)

    Includes: oestrogens, progesterone, androgens; analysed by high -sensitivity liquid chromatography-mass spectrometry (LC-MS)

  9. Body height measured in meters (m)

    Time frame: Only at baseline

    Measured using stadiometer

  10. Change in Body Mass Index (BMI) expressed as kg/m^2

    Time frame: From baseline (day 1) to end of intervention (day 53); additional measurements taken three times a week throughout the intervention duration

    BMI will be calculated using weight and height measures

  11. Change in adipose tissue metabolism assessed by adipocite size

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Measured via abdominal subcutaneous fat biopsy using fine needle aspiration and histomorphometry method

  12. Change in adipose tissue metabolism assessed by phosphorylation of hormone-sensitive lipase (HSL)

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Measured via abdominal subcutaneous fat biopsy using fine needle aspiration and immunoblotting method.

Other outcomes

  1. Change in glycaemic control in response to caloric restriction diet

    Time frame: Every day of the study (days 1-53)

    Measured with continuous glucose monitoring (CGM) Freestyle Libre

  2. Change in fasting concentration of glucose

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Measured from capillary blood from a finger

  3. Change in fasting concentration of ketones

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Measured from capillary blood from a finger

  4. Change in fasting concentration of Glucose Ketone Index (GKI)

    Time frame: From day 8 (start of the maintenance diet) to end of the intervention (day 53)

    Calculated from glucose and ketone values

  5. Change in levels of physical activity (PA) expressed as energy expenditure (kcal/day)

    Time frame: Every day of the study (days 1-53)

    Actigraph wearable device for recording physical activity via accelerometery method

  6. Change in physical activity intensity expressed as minutes spent on Moderate to vigorous (MVPA) per day

    Time frame: Every day of the study (days 1-53)

    Measured accelerometry (with Actigraph wearable device) and calculated using energy expenditure and time spent in MVPA

  7. Change in food intake

    Time frame: Starting from ad libitum intake (days 1-7) and every day of the study diets (day 8-52)

    Measured using weighted intake record

Study contacts

Contact information is provided by the study sponsor or research team.

Alexandra M. Johnstone, Professor

CONTACT

[email protected]

01224 438614

Marta Lonnie, Dr

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University of Aberdeen

Other

Collaborators

  • University of Edinburgh

Registry information

Official study title

GendAge Weight Loss Study: Sex Hormones as Regulators of the Age- and Sex-dependent Benefits of Caloric Restriction

Acronym: GendAge

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jul 15, 2025
Registry last updated
Jul 18, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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