Beta Cell Function in (Pre)Type 1 Diabetes

NCT01402037 | Unknown

• 1 other identifier: KD_BF_02
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

Increased glycemic variability has been proposed as an independent predictor of hypoglycemia in diabetic patients. Likewise, episodes of dysglycemia have been found to be predictive of diabetes in antibodypositive nondiabetic individuals. We hypothesise that an in-depth observational study comparing state-of-the-art measures of functional beta cell mass and glycemic variability will specify the relationship between both variables over a broad range of residual function and will identify treatment goals for functional beta cell mass to be reached in future beta cell therapy trials in order to avoid frequent hypoglycemia in patients and dysglycemia in risk groups. The available expertise and infrastructure (see background and (inter)national context) place the promoters of the present project in a unique position to carry out the planned experiments and support their feasibility.

Conditions

Type 1 Diabetes

Keywords

type 1 diabetes; Prevention; First degree relatives; High risk for type 1 diabetes

Outcome Measures

Primary Outcomes (1)

• evaluate the hyperglycemic clamp to measure the functional beta cell mass test

  to measure the functional beta cell mass of participants as determined by AUC C-peptide release during hyperglycemic clamp test

  2 years

Secondary Outcomes (2)

• Follow up of OGTT's and HbA1c levels in high risk first degree relatives and patients

  2 years

• evaluate the continuous glucose monitoring to measure within- and between-day glycemic variability

  2 years

Study Arms (4)

NDP 12-39 y

OTHER

In newly diagnosed patients a hyperglycemic clamp tests will be performed within 4 weeks after diagnosis and 6, 12, 18 and 24 months later in 40 patients. The clamp will not be carried out in participants who became Cpeptide negative (defined as AUC C-peptide ≤ 0.03 nmol/L x min.) at a previous visit. HbA1c will be determined at the day of the clamp and glycemic variability during 5 days starting immediately after the clamp procedure. Insulin requirements and severe hypoglycemia (defined as an episode in which a patient required the assistance of another person and which was associated with a blood level of \< 50 mg/dL or prompt recovery following intravenous glucose, glucagon or oral carbohydrate) will be recorded

Drug: Glucose; Device: Continuous glucose monitoring

NDP 5-12 y

OTHER

Ten childhood-onset patients (under age 12) will be tested for 5 days with CGM (without clamp) and their glycemic variability compared with that of 10 patients aged 12-17 years at diagnosis.

Device: Continuous glucose monitoring

FDR 12-39 y

OTHER

In first degree relatives of type 1 diabetes patients a hyperglycemic clamp tests will be performed at inclusion and 6, 12, 18 and 24 months later in 40 high-risk first-degree relatives (see previous definition) with a non-diabetic OGTT performed 1 to 2 weeks before the clamp procedure. An OGTT result suggestive of diabetes will be confirmed and the relative will be offered participation in the patient arm of the study. HbA1c will be determined at the day of the OGTT and glycemic variability during the 5 days preceding the OGTT procedure.

Drug: Glucose; Device: Continuous glucose monitoring

FDR 5-12 y

OTHER

Ten high-risk first-degree relatives (see criteria) aged 5 to 12 years will also be tested for CGM and their results correlated with beta-cell function derived from a "mini-clamp" procedure (first 10 min. C-peptide release in hyperglycemic clamp) and results (CGM and first clamp phase) from relatives aged 12-17 years.

Drug: Glucose; Device: Continuous glucose monitoring

Interventions

Glucose DRUG

Glucose 20% intravenous

Also known as: Stimulated glucose

FDR 12-39 y; FDR 5-12 y; NDP 12-39 y

Continuous glucose monitoring DEVICE

Blood glucose profiles: during 5 days glucose profiles will be determined by seven-point self-monitoring of blood glucose (SMBG) (pre-breakfast: assumed time 7 am, post-breakfast: 8.30 am, pre-lunch: 12 am, post-lunch: 1.30 pm, pre-supper: 6 am, post-supper: 7.30 pm, bedtime: 10 pm) and by continuous glucose monitoring (CGM). Participants will be blinded for the CGM results.

Also known as: CGM

FDR 12-39 y; FDR 5-12 y; NDP 12-39 y; NDP 5-12 y

Eligibility Criteria

• Age: 5 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Type 1 diabetic patients:
• aged 12-39 years at diagnosis
• treated with insulin for less than 4 weeks
• optimally treated with intensified insulin treatment: minimal three preprandial injections of ultra-rapidly acting analogs and one evening injection of long-acting insulin (Lantus®, Sanofi Aventis)
• positive for autoantibodies against insulin (IAA-sampled within the first week of insulin treatment), 65kDa glutamate decarboxylase (GADA), IA-2 protein (IA-2A) and/or zinc transporter 8 (ZnT8A)
• First-degree relatives:
• sibling or offspring of a type 1 diabetic patient diagnosed before age 35 or between age 35 and 50 with in addition a body mass index \< 28 kg/m2 and an initial insulin dose \> 0.25 U.kg -1.d-1
• \> 50% risk of diabetes within 5 years as indicated by positivity for at least 2 diabetes antibodies including IA-2A and/or ZnT8A in absence of protective HLA-DQ genotypes (6)

You may not qualify if:

• pregnancy or lactation in women
• use of illicit drugs or overconsumption of alcohol or history of drug or alcohol abuse
• being legally incapacitated, having significant emotional problems at the time of the study, or having a history of psychiatric disorders
• having received antidepressant medications during the last 6 months
• treatment with immune modulating or diabetogenic medication (such as corticosteroids)
• history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the subjects
• patients not treated with Lantus as insulin therapy.

Sponsors & Collaborators

• AZ-VUB: lead
• Vrije Universiteit Brussel: collaborator
• University Hospital, Ghent: collaborator
• University Hospital, Antwerp: collaborator

Study Sites (3)

UZ Brussels

Brussels, 1090, Belgium

RECRUITING

UZ Antwerpen

Edegem, 2650, Belgium

RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Glucose; Continuous Glucose Monitoring

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Investigative Techniques

Study Officials

• Frans K Gorus, MD. PhD.

  UZ Brussels

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frans K Gorus, MD PhD

CONTACT

+32 2 477 50 31

Ursule Van de Velde

CONTACT

+32 2 476 35 46; ursule.vandevelde@uzbrussel.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: July 7, 2011
• First Posted: July 26, 2011
• Study Start: July 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2016
• Last Updated: December 30, 2013

Record last verified: 2013-12

Locations

BE (3)