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NCT Number: NCT06377254

Multi-organ Responses to CHronic Physical Activity and INactivity

Life expectancy has been increasing for the last 150 years, but the maintenance of health has not kept pace with increased lifespan, and on average, UK adults spend the last decade of life in poor-health, with major consequences for society and the individual.

Persistent physical inactivity is thought to be a key contributing factor to the risk of poor health and functional decline occurring in middle-aged and older adults. It is therefore concerning that most middle-aged adults spend >8hrs/day being sedentary, with average step count of 3000-4000 steps/day.

To be able to holistically assess the effectiveness of future strategies to address age-related decline in health, and devise public health messages to help individuals reach older age in better health, it is essential that the complex physiological effects that activity and inactivity have across biological systems are characterised.

The goal of this intervention study is to compare the impact of physical activity and inactivity on body functioning. Twenty moderately active participants will decrease their physical activity for three months to match the average amount carried out by middle-aged people in the UK. They will then undertake 3-months of reconditioning training to restore their fitness. In addition, twenty sedentary participants will increase their physical activity to UK recommended levels for six months.

Before and at points during the intervention period, participants will be asked to make some measurements at home and attend the University of Nottingham to have multiple assessments made. These include;

* fitness, muscle strength and function tests, * completion of questionnaires and computer-based brain puzzles * having muscle and fat tissue biopsies and blood samples taken. * The study also involves having MRI scans.

This 5-year study will commence in January 2024, with participant recruitment starting in March 2024 and finishing in May 2027.

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Key information

Conditions

Sedentary Behavior Age-Related Sarcopenia Age-related Cognitive Decline Behavior Body Weight Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Metabolic Syndrome Motor Activity Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

50 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

David Greenfield Human Physiology Unit

Nottingham, Notts, NG72UH, United Kingdom

Location status: Recruiting

Location contact

Abhishek Sheth, MD

SUB_INVESTIGATOR

Alena Ponitzova

SUB_INVESTIGATOR

Donald Peden, PhD

SUB_INVESTIGATOR

Joanne Mallinson, PhD

CONTACT

[email protected]

+44(0)1158230434

Joanne Mallinson, PhD

SUB_INVESTIGATOR

Liz Simpson, PhD

SUB_INVESTIGATOR

Paul Greenhaff, PhD

PRINCIPAL_INVESTIGATOR

Penny Gowland, PhD

SUB_INVESTIGATOR

Rosemary Nicholls, PhD

SUB_INVESTIGATOR

Sara Brown

CONTACT

[email protected]

+44(0)115 8230434

Sara Brown

SUB_INVESTIGATOR

Sue Francis, PhD

SUB_INVESTIGATOR

About this study

This is a parallel design study comparing the impact of physical activity and inactivity on the way the body functions, to understand the mechanisms (including the inter-relationship between tissues and organs) by which lifestyle behaviours may effect health and wellbeing in later life. In particular, the mechanisms by which inactivity results in long term poor health is not well understood, and has rarely been studied in an integrated way in people. However, initial research indicates that the physiology of being inactive is not simply the reverse of being active. To enable effective treatments and public health advice to be devised so that more adults reach old age in better health, and maintain a good quality of life for a greater proportion of their older age, it is important that the impact of physical inactivity on the way the body functions is better understood. Therefore, twenty participants who are moderately, but not highly active will be asked to decrease their physical activity for three months to match the average exercise levels of middle-aged people in the United Kingdom (UK). This will require them to increase their daily sitting time to 7 hours a day and reduce their step count to <4500 steps per day. At the end of the 3-months they will undertake 3-months of supervised reconditioning training by attending the Medical School at Queen's Medical Centre, Nottingham, three times a week.

In addition, twenty participants who currently have low physical activity levels will be asked to increase their physical activity to UK recommended levels by attending the Medical School at Queen's Medical Centre, Nottingham, three times a week for six months to undertake a supervised exercise program.

Before and during the 6-month period (at weeks 6, 12, 18 and 24) participants will be asked to make some measurements at home (physical activity levels, dietary intake) and attend the University of Nottingham over 4 days to have multiple assessments made. These include: height; weight; body composition (body fat and lean tissue); blood pressure; fitness, muscle strength and function; sleep quality, quality of life and wellbeing (questionnaires). The rate of muscle protein breakdown and muscle protein synthesis, blood sugar regulation, and biochemistry of the blood, fat tissue and muscles will be assessed, and to enable this muscle and fat tissue biopsies will be collected and blood samples taken. The study also involves having MRI scans to study the structure and function of the brain and heart, and to determine liver and muscle fat content.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Group 1 ('non-sedentary') self-reporting <6 sedentary hrs/day, not actively involved in exercise training or a regular physical activity regimen (>8,000 steps/day).
  • Group 2 ('sedentary') self-reporting ≥8 waking hrs/day in sedentary activities and/or ≤5,000 steps/day.
  • Aged 50-65y.
  • Overweight (BMI 25-35 kg/m2).
  • Waist circumference ≥94cm (males) and ≥80cm (females).
  • Willing to alter physical activity levels as instructed for 6 months
  • Without neurological or psychiatric diseases, motor or cognitive restrictions
  • Ability to give informed consent

Exclusion criteria

  • Regular medication use that could interfere with measures
  • A history, or evidence, of chronic cardiovascular, metabolic, musculoskeletal, renal or respiratory diseases.
  • Experiencing 'long-COVID', inflammatory bowel disease or malignancy.
  • Uncontrolled hypertension. Stage 1 hypertension (BP ≤160/100mmHg) with no other signs of cardiovascular disease, and blood pressure (BP) managed by routine medication will not be an exclusion.
  • People employed in jobs that would preclude reducing step count and night-shift workers.
  • Females who are pre/peri-menopausal, (due to effect of oestrogen fluctuations on primary outcomes and the longitudinal study design), but individuals stable on hormone replacement therapy are eligible.
  • Contraindications for MRI.
  • Allergy or sensitivity to local anaesthesia, or dressing adhesive

Treatment and study plan

Decreased Physical Activity

Behavioral

Physical activity levels will be decreased

Increased Physical activity

Behavioral

Physical activity levels will be increased

Primary outcomes

  1. Change in Cardiorespiratory fitness (VO2 max)

    Time frame: 12 weeks

    change in maximal oxygen uptake (continuous incremental bicycle ergometer exercise test with on-line gas analysis) measured every 6 weeks

Secondary outcomes

  1. Change in Isometric leg strength

    Time frame: 24 weeks

    Change in Isometric leg strength measured every 6 weeks using CYBEX dynamometer

  2. Change in time to leg fatigue

    Time frame: 24 weeks

    Change in time taken to induce muscle fatigue measured every 6 weeks using isokinetic knee extensions on a CYBEX dynamometer

  3. Change in incremental area under the curve (iAUC) for blood glucose concentration

    Time frame: 24 weeks

    Change in 180 minute blood glucose concentration incremental area under the curve measured every 6 weeks during an oral glucose tolerance test.

  4. Change in iAUC for serum insulin concentration

    Time frame: 24 weeks

    Change in 180-minute serum insulin concentration incremental area under the curve measured every 6 weeks during an oral glucose tolerance test

  5. Change in fasting glucose oxidation rate

    Time frame: 24 weeks

    Change in glucose oxidation rate (when fasted), measured every 6 weeks using ventilated hood indirect calorimetry

  6. Change in 'fed' glucose oxidation rate

    Time frame: 24 weeks

    Change in glucose oxidation rate (in the insulin-stimulated 'fed' state), measured every 6 weeks using ventilated hood indirect calorimetry during an oral glucose tolerance test

  7. Change in Short Form Health Survey (SF36) Questionnaire aggregated normalised 'physical' score

    Time frame: 24 weeks

    Change in 'SF36' Questionnaire aggregated 'physical' score (normalised to UK population) calculated according to standard procedures (min 0, max 100), with higher score indicating better physical wellbeing measured every 6 weeks

  8. Change in Short Form Health Survey (SF36) Questionnaire aggregated and normalised 'mental' score

    Time frame: 24 weeks

    Change in 'SF36' Questionnaire aggregated 'mental' score (normalised to UK population) calculated according to standard procedures (min 0, max 100), with higher score indicating better mental wellbeing, measured every 6 weeks

  9. Change in World Health Organisation Quality of Life (WHOQoL) score

    Time frame: 24 weeks

    Change in World Health Organisation Quality of Life Score (measured using the WHOQoL-Bref questionnaire every 6 weeks), (min score 0, max 100), with higher score indicating a better state of health.

  10. Change in Pittsburgh Sleep Quality Index (PSQI)

    Time frame: 24 weeks

    Change in PSQI score (min score 0, max 21), measured every 6 weeks, with higher score indicating poorer sleep quality

  11. Change in Stroop test; % Accuracy

    Time frame: 24 weeks

    Change in the percentage of accurate responses, measured every 6 weeks, with higher score indicating better cognitive performance. Minimum value 0%, maximum value 100%

  12. Change in Stroop test; reaction time

    Time frame: 24 weeks

    Change in the reaction time for responses, measured every 6 weeks, with higher score indicating slower cognitive performance. No minimum or maximum value defined.

  13. Change in four-choice reaction time test; % Accuracy

    Time frame: 24 weeks

    Change in the percentage of accurate responses, measured every 6 weeks, with higher score indicating better cognitive performance. Minimum value 0%, maximum value 100%

  14. Change in four-choice reaction time test; reaction time

    Time frame: 24 weeks

    Change in the reaction time for responses, measured every 6 weeks, with higher score indicating slower cognitive performance. No minimum or maximum value defined.

  15. Change in card sort test; % Accuracy

    Time frame: 24 weeks

    Change in the percentage of accurate responses, measured every 6 weeks, with higher score indicating better cognitive performance. Minimum value 0%, maximum value 100%

  16. Change in card sort test; reaction time

    Time frame: 24 weeks

    Change in the reaction time for responses, measured every 6 weeks, with higher score indicating slower cognitive performance. No minimum or maximum value defined.

  17. Change in Logical reasoning test; % accuracy

    Time frame: 24 weeks

    Change in the accuracy of responses, measured every 6 weeks, with higher score indicating better cognitive performance. Minimum value 0%, maximum value 100%

  18. Change in Logical reasoning test; reaction time

    Time frame: 24 weeks

    Change in the reaction time for responses, measured every 6 weeks, with higher score indicating slower cognitive performance. No minimum or maximum value defined.

  19. Change in serial subtractions test; number of responses in 2 minutes

    Time frame: 24 weeks

    Change in the number of responses, measured every 6 weeks, with higher score indicating better cognitive performance. minimum number is 0, maximum number is variable dependent on starting value (800-999; randomly selected by computer program) and speed of response.

  20. Change in Corsi blocks test; score

    Time frame: 24 weeks

    Change in the test score, measured every 6 weeks, with higher score indicating better cognitive performance.Minimum score is 0 and maximum is 15.

  21. Change in Muscle protein synthesis rate

    Time frame: 24 weeks

    Muscle synthesis protein rate calculated from deuterium incorporation into muscle tissue

  22. Change in Muscle protein breakdown rate

    Time frame: 24 weeks

    Muscle protein breakdown rate calculated every 6 weeks using 3-methylhistidine tracer

  23. Change in whole body fat volumes

    Time frame: 24 weeks

    Change in the amount of fat within the body, measured every 6 weeks using magnetic resonance imaging (MRI)

  24. Change in liver fat volumes

    Time frame: 24 weeks

    Change in the amount of fat within the liver, measured every 6 weeks using magnetic resonance imaging (MRI)

  25. Change in thigh muscle fat volumes

    Time frame: 24 weeks

    Change in the amount of fat within the vastus lateralis thigh muscle, measured every 6 weeks using magnetic resonance imaging (MRI)

  26. Change in whole body muscle volumes

    Time frame: 24 weeks

    Change in the amount of muscle within the body, measured every 6 weeks using magnetic resonance imaging (MRI)

  27. Change in muscle phosphocreatine synthesis rate

    Time frame: 24 weeks

    Change in the rate of phosphocreatine synthesis, measured every 6 weeks using magnetic resonance spectroscopy

  28. Change in cerebral volume

    Time frame: 24 weeks

    Change in the volume of brain tissue, measured every 6 weeks using magnetic resonance imaging (MRI)

  29. Change in cortical thickness

    Time frame: 24 weeks

    Change in the thickness of the brain cortex, measured every 6 weeks using magnetic resonance imaging (MRI)

  30. Change in plasma metabolome

    Time frame: 24 weeks

    change in untargeted plasma metabolome profile measured every 6 weeks

Other outcomes

  1. Fasting blood lipid concentration

    Time frame: pre-intervention

    concentration of lipid within the blood

  2. Fasting blood lipid concentration

    Time frame: 6 weeks

    concentration of lipid within the blood

  3. Fasting blood lipid concentration

    Time frame: 12 weeks

    concentration of lipid within the blood

  4. Fasting blood lipid concentration

    Time frame: 18 weeks

    concentration of lipid within the blood

  5. Fasting blood lipid concentration

    Time frame: 24 weeks

    concentration of lipid within the blood

  6. liver function test: alanine transaminase (ALT)

    Time frame: pre-intervention

    concentration of ALT measured on blood sample

  7. liver function test: alanine transaminase (ALT)

    Time frame: 6 weeks

    concentration of ALT measured on blood sample

  8. liver function test: alanine transaminase (ALT)

    Time frame: 12 weeks

    concentration of ALT measured on blood sample

  9. liver function test: alanine transaminase (ALT)

    Time frame: 18 weeks

    concentration of ALT measured on blood sample

  10. liver function test: alanine transaminase (ALT)

    Time frame: 24 weeks

    concentration of ALT measured on blood sample

  11. liver function test: aspartate aminotransferase (AST)

    Time frame: pre-intervention

    concentration of AST measured on blood sample

  12. liver function test: aspartate aminotransferase (AST)

    Time frame: 6 weeks

    concentration of AST measured on blood sample

  13. liver function test: aspartate aminotransferase (AST)

    Time frame: 12 weeks

    concentration of AST measured on blood sample

  14. liver function test: aspartate aminotransferase (AST)

    Time frame: 18 weeks

    concentration of AST measured on blood sample

  15. liver function test: aspartate aminotransferase (AST)

    Time frame: 24 weeks

    concentration of AST measured on blood sample

  16. liver function test: Bilirubin

    Time frame: pre-intervention

    concentration of bilirubin measured on blood sample

  17. liver function test: Bilirubin

    Time frame: 6 weeks

    concentration of bilirubin measured on blood sample

  18. liver function test: Bilirubin

    Time frame: 12 weeks

    concentration of bilirubin measured on blood sample

  19. liver function test: Bilirubin

    Time frame: 18 weeks

    concentration of bilirubin measured on blood sample

  20. liver function test: Bilirubin

    Time frame: 24 weeks

    concentration of bilirubin measured on blood sample

  21. liver function test: Albumin

    Time frame: pre-intervention

    concentration of albumin measured on blood sample

  22. liver function test: Albumin

    Time frame: 6 weeks

    concentration of albumin measured on blood sample

  23. liver function test: Albumin

    Time frame: 12 weeks

    concentration of albumin measured on blood sample

  24. liver function test: Albumin

    Time frame: 18 weeks

    concentration of albumin measured on blood sample

  25. liver function test: Albumin

    Time frame: 24 weeks

    concentration of albumin measured on blood sample

  26. liver function test: Gamma glutamyl transferase (GGT)

    Time frame: pre-intervention

    concentration of GGT measured on blood sample

  27. liver function test: Gamma glutamyl transferase (GGT)

    Time frame: 6 weeks

    concentration of GGT measured on blood sample

  28. liver function test: Gamma glutamyl transferase (GGT)

    Time frame: 12 weeks

    concentration of GGT measured on blood sample

  29. liver function test: Gamma glutamyl transferase (GGT)

    Time frame: 18 weeks

    concentration of GGT measured on blood sample

  30. liver function test: Gamma glutamyl transferase (GGT)

    Time frame: 24 weeks

    concentration of GGT measured on blood sample

  31. Blood Haemoglobin concentration

    Time frame: pre intervention

    haemoglobin concentration measured on a blood sample

  32. Blood Haemoglobin concentration

    Time frame: 6 weeks

    haemoglobin concentration measured on a blood sample

  33. Blood Haemoglobin concentration

    Time frame: 12 weeks

    haemoglobin concentration measured on a blood sample

  34. Blood Haemoglobin concentration

    Time frame: 18 weeks

    haemoglobin concentration measured on a blood sample

  35. Blood Haemoglobin concentration

    Time frame: 24 weeks

    haemoglobin concentration measured on a blood sample

Study contacts

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

Melanie Tooley (participant recruitment), BSc

CONTACT

[email protected]

+44 (0) 115 9515151 ext. 19105

Paul L Greenhaff (PI), PhD

CONTACT

[email protected]

+44 (0) 1158230133

Sponsors and collaborators

Lead sponsor

University of Nottingham

Other

Collaborators

  • Biotechnology and Biological Sciences Research Council

Registry information

Official study title

Concurrent Multi-organ Responses to CHronic Physical Activity and INactivity Intervention, to Increase Research Discovery in Human Health and Wellbeing

Acronym: CHAIN

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Apr 22, 2024
Registry last updated
Dec 4, 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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