Effects of Reactive Hypoglycaemia on Cognition in Earlier or Later Chronotypes

NCT06941740 | Enrolling By Invitation DMC

• 1 other identifier: BU 1807/8-1-2
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

Brief Summary

Studies suggest a link between lower postprandial glycaemic response and better cognitive performance in children, adolescents, and young adults, though evidence remains inconclusive. High glycaemic index (GI) meals quickly raise blood glucose, potentially causing reactive hypoglycaemia (glucose levels below baseline) and harming cognitive performance, especially in the late postprandial period, particularly after 120 minutes. Young adults may be more sensitive to these cognitive effects due to morning circadian misalignment, as their sleep midpoint (chronotype) is biologically most delayed. Recent research suggests that those with later chronotypes do not display the known circadian decline in glucose tolerance as indicated by equally high glycaemic responses to the same high GI meal in the morning or the evening. Eating breakfast "against the inner clock" may harm glycaemic response, particularly for those with a later chronotype. Those with morning circadian misalignment may also limit breakfast to beverages. Reactive hypoglycaemia commonly follows beverage consumption, especially soft drinks, energy drinks, glucose solutions, and low-GI fruit juices, occurring within 60 minutes after consumption. Later chronotypes may be more prone to reactive hypoglycaemia from drinks, harming cognition. This nutrition trial aims to investigate (I) the effects of breakfast-induced reactive hypoglycaemia on memory and attention in young, healthy, non-obese university students and (II) the relevance of chronotype to hypoglycaemia occurrence. To study reactive hypoglycaemia, a low GI beverage will be used, causing hypoglycaemia despite a low glycaemic response. Two samples will be examined: students of early and late chronotype. Postprandial insulin and cortisol changes will be analyzed, as improved insulin sensitivity and cortisol levels seem to affect cognition. From October 2024 to January 2025, 356 students (ages 18-25) enrolled in the GlyCoBrain Observational study (ID: NCT06679088) and were screened for chronotypes at Paderborn University. Participants with extreme chronotypes will be invited to this crossover study. Power calculations indicated a sample of 88 participants who complete both intervention days. They will consume a low-GI beverage at 9 a.m. causing reactive hypoglycaemia (glucose-fructose-sucrose solution) or a non-hypoglycaemia causing beverage (isomaltulose® solution) and undergo repeated cognitive assessments for the following 180 minutes.

Conditions

Healthy

Keywords

chronotype; breakfast; continuous glucose monitoring; MCTQ; memory; attention; cognition; body composition; glycaemic index; reactive hypoglycaemia

Outcome Measures

Primary Outcomes (1)

• Difference in immediate memory between low-GI breakfast

  Computer-assisted cognition test

  On the first intervention day and after one week from -30 until 150 minutes after intervention focusing on 90 minutes (when reactive hypoglycaemia is expected to manifest)

Study Arms (2)

low-GI beverage causing reactive hypoglycaemia

EXPERIMENTAL

low-GI beverage causing reactive hypoglycaemia consisting of 75 g glucose-fructose-sucrose dissolved in 500 ml tap water

Other: immediate verbal memory after low glycemic index breakfast inducing no reactive hypoglycaemia; Other: immediate verbal memory after low glycemic index breakfast causing reactive hypoglycaemia

low-GI beverage not inducing reactive hypoglycaemia

EXPERIMENTAL

low-GI beverage not inducing reactive hypoglycaemia consisting of 75 g isomaltulose dissolved in 500 ml tap water

Other: immediate verbal memory after low glycemic index breakfast inducing no reactive hypoglycaemia; Other: immediate verbal memory after low glycemic index breakfast causing reactive hypoglycaemia

Interventions

immediate verbal memory after low glycemic index breakfast inducing no reactive hypoglycaemia OTHER

\- Difference in immediate verbal memory after low GI breakfast without reactive hypoglycaemia at 90minutes

low-GI beverage causing reactive hypoglycaemia; low-GI beverage not inducing reactive hypoglycaemia

immediate verbal memory after low glycemic index breakfast causing reactive hypoglycaemia OTHER

\- Difference in immediate verbal memory after low GI breakfast causing reactive hypoglycaemia at 90 minutes

low-GI beverage causing reactive hypoglycaemia; low-GI beverage not inducing reactive hypoglycaemia

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants of GlyCoBrain Observational Study
• Early or late chronotype (approx. lowest and highest quartile)

You may not qualify if:

• Students studying nutritional science or home economics (study programs of the study PI)
• Intermediate chronotypes
• Persons unwilling to abstain from smoking or cannabis use during the intervention period
• Persons unwilling to consume standard evening meals before intervention days
• BMI\>30 kg/m² (diurnal variation in glycaemic control is known to be absent among persons with obesity) and \<18.5 kg/m2 (since underweight is also known to affect glucose homeostasis)
• acute or permanent use of sleep-promoting medications (including herbal preparation):
• medications: melatonin, diphenhydramine, doxylamine
• herbal preparations: hops, St. John's wort, lemon balm, lavender, passionflower, Baldurat, Neurexan, cannabinoids
• Use of psychotropic medications (antidepressants, tranquillizers, antipsychotics)
• Use of methylphenidate (e.g. Ritalin, Medikinet, Concerta)
• Use of cannabinoids by prescription
• Continuous administration of antihistamines when discontinuation is not feasible during the intervention
• Use of herbal preparations affecting memory and concentration (e.g. ginkgo, ginseng, ashwagandha)
• Use of other medications (e.g. insulin, metformin, SGLT2 inhibitors, steroids, ACE inhibitors)
• Selected chronic diseases (depression and other mental disorders such as anxiety disorder, ADHD, diabetes mellitus (all types), prediabetes, blood clotting disorders (e.g., thrombocytopenia, haemophilia), eating disorders (e.g., anorexia, binge eating, bulimia), Chronic inflammatory bowel diseases, infectious diseases (HIV, hepatitis), Addiction disorders (e.g., alcohol, drug, or medication dependency)

Sponsors & Collaborators

• Anette Buyken: lead
• Paderborn University: collaborator
• University of Southern Denmark: collaborator

Study Sites (1)

Paderborn University

Paderborn, North Rhine-Westphalia, 33098, Germany

Location

Related Publications (26)

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MeSH Terms

Conditions

Hypoglycemia

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Lars Libuda, Prof. Dr., Prof. Dr.

  Paderborn University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study is double-blind, meaning that neither participants nor researchers know which of the two low-GI beverages they are consuming. Beverages will be pre-prepared by staff who are not involved in its provision.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: It is estimated that a maximum of 177 participants will need to be invited to obtain full data sets from 44 participants of an earlier chronotype and 44 of a later chronotype each completing the cross-over designed intervention study. The intervention study consists of the consumption of one of two low-GI beverages at 09:00 a.m., with one of these beverages ("glucose-fructose-sucrose beverage") inducing reactive hypoglycaemia and the other not ("isomaltulose beverage"). The participants will be randomly assigned to receive one of the two beverages on the first intervention day and the other on the second intervention day. The trial is a two-arm crossover study. Each participant serves as his or her own control, thus accounting for interindividual variations in diurnal glycaemic responses and cognitive performance.

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: April 24, 2025
• Study Start: April 4, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)