Cognition in Patients With Hypoglycemia, Without Diabetes

Pilot Study - Cognition in Patients With Hypoglycemia, Without Diabetes

The purpose of this study is to determine if there is a relationship between recurrent hypoglycemia (low blood sugar) and cognition (thinking) in individuals who have a history of hypoglycemia, but do not have pre-diabetes or diabetes.

This study will analyze whether recurrent hypoglycemia is associated with differences in cognition (thinking), and if individuals with a history of hypoglycemia perform less well on cognitive assessments compared to individuals without known hypoglycemia.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypoglycemia; Cognition
• Intervention / Treatment: Other: Cognitive Assessment (not diagnostic); Diagnostic test: ECG

Detailed Description

This study will test the hypothesis that recurrent hypoglycemia is associated with differences in cognition (thinking), by analyzing results of cognitive testing in individuals with a history of hypoglycemia as compared with those without known hypoglycemia.

This pilot study will identify cognitive domains of interest in participants with hypoglycemia, as well as inform the development of a future battery of assessments, which could be replicated in a larger sample. Cognitive domains which will be assessed include: memory, language, executive function, and psychomotor speed.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited into 4 groups: (1) patients with hypoglycemia after upper gastrointestinal surgery, recruited from the Joslin Hypoglycemia Clinic, (2) asymptomatic post-bariatric patients, recruited from postoperative surgical clinics at Brigham and Women's Hospital, (3) patients with hypoglycemia and no history of upper gastrointestinal surgery, and no current diagnosis of diabetes or pre-diabetes, recruited from the Joslin Hypoglycemia Clinic, (4) participants without hypoglycemia or upper gastrointestinal surgery (controls), recruited by local advertisement.

Some participants may be recruited from other hypoglycemia studies at Joslin.

Description

Inclusion Criteria:

1. Age 18-70 years of age, inclusive, at screening.
2. Willingness to provide informed consent and attend one study visit.
3. For hypoglycemia after upper GI surgery group: Males or females diagnosed with ongoing post upper GI surgery hypoglycemia, with prior episodes of neuroglycopenia, unresponsive to dietary intervention.
4. For hypoglycemia without a history of upper gastrointestinal surgery group: Males or females diagnosed with ongoing hypoglycemia with prior episodes of neuroglycopenia, and without a history of prediabetes, diabetes, or upper GI surgery.
5. For post-bariatric without hypoglycemia group: Males or females with history of bariatric surgery, and no history of symptomatic hypoglycemia.
6. For non-surgical controls only: Males or females with no history of upper GI surgery and no history of hypoglycemia, prediabetes, or diabetes.

Exclusion Criteria:

1. Active treatment with any diabetes medications, except for acarbose.
2. History of cerebrovascular accident.
3. History of a traumatic brain injury not related to hypoglycemia.
4. Active depression.
5. Active alcohol abuse or substance abuse.
6. Known insulinoma, gastrinoma or other neuroendocrine tumor.
7. Having undergone same / similar cognitive assessments within the last calendar year.

There will be no involvement of special vulnerable populations such as fetuses, neonates, pregnant women, children, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable populations.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hypoglycemia after upper gastrointestinal (GI) surgery; Participants with hypoglycemia after upper GI surgery, recruited from the Joslin Hypoglycemia Clinic and from other hypoglycemia studies at Joslin.	Other: Cognitive Assessment (not diagnostic); Cognitive testing will assess working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.; Diagnostic test: ECG; ECG will take place during screening visit.; Other Names: Electrocardiogram (ECG)
Asymptomatic post-bariatric participants; Participants with a history of bariatric surgery, but without a diagnosis of hypoglycemia, or symptoms of hypoglycemia. They will be recruited by advertisement flyers at postoperative surgical clinics at local hospitals (e.g. Brigham and Women's and Beth Israel Deaconess Hospitals) and from other hypoglycemia studies at Joslin.	Other: Cognitive Assessment (not diagnostic); Cognitive testing will assess working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.; Diagnostic test: ECG; ECG will take place during screening visit.; Other Names: Electrocardiogram (ECG)
Hypoglycemia no upper GI surgery & no diabetes (DM) or pre-DM; Participants with hypoglycemia and no history of upper gastrointestinal surgery, and NO current diagnosis of diabetes or pre-diabetes, recruited from the Joslin Hypoglycemia Clinic, or from other hypoglycemia studies at Joslin.	Other: Cognitive Assessment (not diagnostic); Cognitive testing will assess working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.; Diagnostic test: ECG; ECG will take place during screening visit.; Other Names: Electrocardiogram (ECG)
Controls, no hypoglycemia or history of upper GI surgery; Participants without hypoglycemia or upper gastrointestinal surgery (controls), recruited by local advertisement. Some participants may be recruited from other hypoglycemia studies at Joslin.	Other: Cognitive Assessment (not diagnostic); Cognitive testing will assess working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.; Diagnostic test: ECG; ECG will take place during screening visit.; Other Names: Electrocardiogram (ECG)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of verbal memory	Rey Auditory Verbal Learning Test (RAVLT) immediate recall accuracy scores will be used to measure verbal memory. Scores will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025
Assessment of delayed memory	RAVLT 20 minute recall accuracy scores, will be used to measure delayed memory and will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025
Assessment of working memory	Letter-Number Sequencing subtest from the Wechsler Memory Scale III scores will be used to measure working memory and will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of cognitive flexibility using trail making tasks	Delis-Kaplan Executive Function System (DKEFS),Trail Making Task scores will be used to assess the cognitive flexibility component of executive function. Scores are derived from time to complete the task plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025
Assessment of multitasking	DKEFS Trail Making Task scores will be used to assess the multitasking component of executive function. Scores are derived from time to complete the task, plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025
Assessment of cognitive flexibility using color-word inference test	DKEFS Color-Word Interference Test (CWIT) scores will be used to measure the cognitive flexibility component of executive function. The CWIT is scored by time to complete plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025
Assessment of inhibition	DKEFS CWIT scores will be used to measure the inhibition component of executive function. The CWIT is scored by time to complete plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025
Assessment of verbal ability cognitive control	DKEFS Verbal Fluency Task will be used to assess the verbal functioning cognitive control ability component of executive function. Scores are derived from the number of unique, correct words. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025
Assessment of psychomotor speed	The Grooved Peg Board test will be used to assess psychomotor speed. It is scored according to time for completion combined with the number of dropped pegs. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.	March 2025

Collaborators and Investigators

• Sponsor: Joslin Diabetes Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 4, 2020
• Primary Completion (ANTICIPATED): April 30, 2023
• Study Completion (ANTICIPATED): April 30, 2023

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (ACTUAL): June 12, 2020

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Memory; Executive Function; Post-Bariatric Hypoglycemia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia
• Other Study ID Numbers: 00000098

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No