Carotid Body Function in Type 2 Diabetes Mellitus (CBHypoxia)

Carotid Body Dysfunction in Type 2 Diabetes

This trial will assess chemosensitivity differences of the carotid bodies in individuals with T2DM, compared to healthy controls. During baseline and hyperinsulinemia.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Hypoxia
• Intervention / Treatment: Diagnostic test: Hyperinsulemic-Euglycemic Clamp & Hypoxic Ventilatory Response (HVR)

Detailed Description

During the COVID-19 pandemic patients with comorbidities such as hypertension, diabetes mellitus, obesity and pregnancy were overrepresented in the population that was admitted to the hospital. Morbidity and mortality due to SARS-COV-2 infection was higher in these patients compared to patients without these comorbidities. The higher incidence, morbidity and mortality is suggestive of an underlying mechanism that puts these patients more at risk. A proposed mechanism is the sympathetic overactivity that is associated with these conditions. Recently, it has become clear that the carotid bodies play an important role in sympathetic overactivity in these conditions. Dysfunction of this organ is associated with decreased chemosensitivity, disruption of insulin sensitivity, but is also associated with changes in neurohumoral control in response to infection. Whether carotid body dysfunction can explain the severity of SARS-COV-2 infection remains to be seen. The aim of this study is to find whether patients with type 2 diabetes have altered chemosensitivity and are in fact sympathetically overactive compared to healthy controls and during a hyperinsulinemic-euglycemic clamp. Findings could help explain why type 2 diabetes patients are more heavily affected by SARS-COV-2 and could identify potential targets for treatment in these patients.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands
      • LUMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• 18 years and older
• Subjects must be willing to give written informed consent for the trial and able to adhere to dose and visit schedule.
• Non-insulin-dependent diabetes mellitus (NIDDM) or healthy sex, age (± 3 yrs) and BMI (± 3 kg/m2) matched controls.
• Have no clinical or electrocardiographic signs of ischemic heart disease as determined by the Investigator with normal cardiac intervals appropriate for their gender. The Screening 12 lead ECG conduction intervals must be within gender specific normal range (e.g., QTcF ≤ 430 msec, PR interval ≤ 220 msec). ECGs are to be judged by the investigator or sub investigator as per standardized procedures.

• Vital sign measurements must be within the following ranges: (Individuals with values outside (or indicate lower or higher) of these ranges may be enrolled if clinically acceptable to the investigator and sponsor.

  • body temperature, between 35.5°C and 37.5°C
  • systolic blood pressure, 90 to 150 mmHg
  • diastolic blood pressure, 40 to 95 mmHg
  • pulse rate, 40 to 100 bpm
• Subjects must be free of any clinically significant disease that would interfere with the study evaluations.
• Subjects presenting out of range values of lab/ECG/vital signs compatible with normal variation of the normal healthy subject can be included in the study at the investigator's discretion and sponsor written approval.
• Positive Allen's test
• Fitzpatrick skin type I or II

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Insulin dependent diabetes mellitus
• Diagnosed Obstructive Sleep Apnea (OSAS) or high suspicion of OSAS determined by a STOP-BANG score > 5
• Respiratory or cardiovascular disease
• Smoking/vaping
• Positive pregnancy test
• conditions that result in elevated levels of methaemoglobinia
• body mass index > 35 kg/m2
• Use of illicit drugs
• Use of prescription opioids or benzodiazepines
• Failure of the drug of abuse tests at screening or check-in.
• History of dyspnea, asthma, tuberculosis, chronic obstructive pulmonary disease, or any other ventilatory / lung disease.
• Subjects with excessive facial hair preventing sealing of the occlusive face mask.
• Subjects who, in the opinion of the investigator, will not be able to participate optimally in the study.
• Subject who has a history of any infectious disease within 4 weeks prior to drug administration that in the opinion of the investigator, affects the subject's ability to participate in the trial.
• Subjects who are part of the study staff personnel or family members of the study staff personnel.
• Subjects who have demonstrated allergic reactions (e.g., food, drug, atopic reactions or asthmatic episodes) which, in the opinion of the investigator and sponsor, interfere with their ability to participate in the trial.
• Personal or family history of arrhythmias or ECG conductance abnormalities.
• Hypokalemia defined as <3.5 mmol/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diabetes Type 2; Patients with DM Type 2 using Oral Diabetes Medications only.	Diagnostic test: Hyperinsulemic-Euglycemic Clamp & Hypoxic Ventilatory Response (HVR); Hyperinsulemic-Euglycemic Clamp as described by deFronzo et al.
Active Comparator: Healthy controls; Healthy controls without comorbidities.	Diagnostic test: Hyperinsulemic-Euglycemic Clamp & Hypoxic Ventilatory Response (HVR); Hyperinsulemic-Euglycemic Clamp as described by deFronzo et al.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemosensitivity of carotid bodies during baseline and euglycemic clamp	L/min/PaO2	5 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRV during baseline and euglycemic clamp	HRV parameters	30 min

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Demcon
• Investigators: Principal Investigator: Albert Dahan, MD, PhD, LUMC

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): August 5, 2022
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Signs and Symptoms, Respiratory; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoxia
• Other Study ID Numbers: NL78476.058.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: On request.

Drug and device information, study documents

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