Physiological and Sensory Responses to Prolonged Fasting in Humans (PRO-FAST)

• ClinicalTrials.gov Identifier: NCT05977569
• Recruitment Status: Active, not recruiting
• First Posted: August 4, 2023
• Last Update Posted: August 4, 2023
• Sponsor: University of Bath
• Collaborator: University of Nottingham
• Information provided by (Responsible Party): James Betts, University of Bath

Tracking Information

• First Submitted Date: September 7, 2021
• First Posted Date: August 4, 2023
• Last Update Posted Date: August 4, 2023
• Actual Study Start Date: June 28, 2021
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 26, 2023)

Change in postprandial insulin responses [ Time Frame: 3 days ]

Change in postprandial insulin (mmol/L) response to a standardised meal before and after 3 days of fasting.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 26, 2023)

• Change in circulating glycerol and non-esterified fatty acids [ Time Frame: 1 day, 2 days, 3 days ]
  Change in indices of lipolysis from adipose tissue in response to prolonged fasting (Glycerol mmol/L; NEFA mmol/L)
• Change in Autophagy [ Time Frame: 3 days ]
  Change in autophagic flux in response to prolonged fasting, assessed in skeletal muscle and circulating neutrophils.
• Change in plasma lactate [ Time Frame: 1 day, 2 days, 3 days ]
  Change in plasma lactate in response to prolonged fasting (indices of Cori cycle)
• Change in plasma pyruvate [ Time Frame: 1 day, 2 days, 3 days ]
  Change in plasma pyruvate in response to prolonged fasting (indices of Cori cycle)
• Change in ketosis. [ Time Frame: 1 day, 2 days, 3 days. ]
  Change in urinary (acetoacetate) ketones in response to prolonged fasting.
• Change in ketosis. [ Time Frame: 1 day, 2 days, 3 days. ]
  Change in circulating (beta-hydroxybutyrate) ketones in response to prolonged fasting.
• Change in body mass [ Time Frame: 1 day, 2 days, 3 days. ]
  Change in body mass, pre-post, and during the prolonged fast.
• Change in blood pressure [ Time Frame: 1 day, 2 days, 3 days. ]
  Change in blood pressure pre-, post-, and during the prolonged fast
• Change in interstitial fluid glucose concentrations [ Time Frame: 1 day, 2 days, 3 days. ]
  Change in interstitial fluid glucose concentrations pre-, post-, and during the prolonged fast (assessed via continual glucose monitoring)
• Change in amino acid metabolism [ Time Frame: 3 days. ]
  Change in amino acid metabolism (i.e. BCAAs and ketoacids) in skeletal muscle
• Change in amino acid metabolism [ Time Frame: 3 days. ]
  Change in amino acid metabolism (i.e. BCAAs and ketoacids) in adipose tissue
• Change in amino acid metabolism [ Time Frame: 3 days. ]
  Change in amino acid metabolism (i.e. BCAAs and ketoacids) in circulation
• Change in postprandial glucose responses. [ Time Frame: 3 days. ]
  Change in postprandial glucose (mmol/L) response to a standardised meal before and after 3 days of fasting.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Physiological and Sensory Responses to Prolonged Fasting in Humans
• Official Title: Physiological and Sensory Responses to Prolonged Fasting in Humans
• Brief Summary: This study aims to establish the metabolic/molecular response in both adipose tissue and skeletal muscle as well as sensory experiences (pain, fatigue, drive) to prolonged fasting of 3 days duration. Participants will undergo sequential meal assessment before and after a 3 day fast with measures taken throughout each fasting day.

Detailed Description

This study will employ a single-arm, non-randomised design in which participants will act as their own control prior to undergoing 3 days of fasting. The control phase includes 3 days of habitual energy balance assessment before coming into the laboratory for baseline meal testing with blood, muscle, and adipose samples as well as anthropometric assessment.

Participants will then be provided with a standardised lunch to be consumed around midday and a standardised dinner to be consumed at 2000 h.

Participants will then be asked to refrain from caloric intake for 3 days until they return to the laboratory for follow up measures.

Participants will be provided with monitoring equipment throughout the 3 days of fasting and will be asked to provide a blood sample at 0800 h each day alongside self recording of blood pressure, weight, and urinary ketones each day. On the middle day (day 2) participants will also be asked to come into the lab to provide a blood sample at 2000 h.

The follow up visit will be identical to that performed before the fast, including meal testing, blood, muscle, and adipose samples.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science

Condition

• Fasting
• Metabolic Disturbance
• Energy Supply; Deficiency
• Adiposity

Intervention

Other: Prolonged Fasting

Participants are asked to refrain from caloric intake for 3 days following a period of habitual lifestyle assessment and metabolic assessment.

Study Arms

Experimental: Prolonged Fasting

All participants are asked to act as their own control prior to being asked to undergo 3 days of fasting.

Intervention: Other: Prolonged Fasting

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 26, 2023): 7
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 30, 2024
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• • Body mass index 20.0-29.9 kg∙m-2

  • Age 18-45 years
  • Willing to abstain from food intake for just over 3 days (~82 hours)
  • Able and willing to provide informed consent and safely comply with study procedures
  • Females to maintain record of regular menstrual cycle phase or contraceptive use
  • No anticipated changes in lifestyle during the study (e.g. holidays or exercise programmes)

Exclusion Criteria:

• • Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias

  • Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes)
  • Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment
  • Pregnancy
  • Breastfeeding
  • Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker)
  • History of eating disorders (e.g. anorexia)
  • Any reported recent (<6 months) change in body mass (± 3%)
  • Uncontrolled hyperthyroidism
  • Advanced cerebrovascular insufficiency or dementia
  • Advanced liver or kidney insufficiency
  • History of migraine and or headache
  • Psychotic disorders
  • Unstable or severe coronary artery disease
  • Retinal detachment
  • Duodenal or stomach ulcer
  • Cancer and malignant disease
  • Regular use of Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Use of Systemic corticoids
  • Use of Antihypertensives (especially beta-blockers and diuretics)
  • Use of Antidiabetics
  • Use of Anti-coagulants
  • Use of Psychotropics (especially neuroleptics and lithium)
  • Use of Anticonvulsants.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT05977569
• Other Study ID Numbers: PF
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: James Betts, University of Bath
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Bath
• Original Study Sponsor: Same as current
• Collaborators: University of Nottingham
• Investigators: Not Provided
• PRS Account: University of Bath
• Verification Date: July 2023