Type 1 DiabetesNCT01402037
Beta Cell Function in (Pre)Type 1 Diabetes
A study testing Glucose and Continuous glucose monitoring in people with Type 1 Diabetes, run by Universitair Ziekenhuis Brussel at 3 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Glucose and Continuous glucose monitoring
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesBelgium
- Study dates
- Jul 2011to Jul 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 39 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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:
Show all 9Show fewer
- aged 12-39 years at inclusion
- 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)
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
Frans K Gorus, MD PhD contact
Belgium3 sites, 3 recruiting
- Recruiting
UZ Brussels
Brussels, 1090
Bart Keymeulen, MD PhD, +32 2 477 61 11, bart.keymeulen@uzbrussel.be
Katelijn Decochez, MD PhD
- Recruiting
UZ Antwerpen
Edegem, 2650
Christophe Deblock, MD. PhD.
Christophe Deblock, MD PhD
- Recruiting
UZ Gent
Ghent, 9000
Johannes Ruige, MD PhD, johannes.Ruige@uzgent.be
Johannes Ruige, MD PhD
About this study
Official title: Relation Between Residual Beta Cell Function and Glycemic Variability in (Pre) Type 1 Diabetes.
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.
Read the detailed description
The established clinical network and the developed dynamic function tests and biological markers provide us with the unique opportunity to identify sufficiently large groups of high-risk first-degree relatives (> 50% risk of diabetes) of a proband with type 1 diabetes and of recent-onset type 1 diabetic patients with the overall aim to investigate the correlation between functional beta cell mass and glycemic variability in relation to metabolic outcome in order to determine thresholds of residual function below which:
- glucose tolerance starts to decline sharply in relatives
- the risk of deteriorating metabolic control and (severe) hypoglycemic events strongly increases in patients
To this effect we will:
- measure and follow over a two-year period
- the functional beta cell mass of participants as determined by AUC C-peptide release - the preferred outcome measure in type 1 diabetes trials during hyperglycemic clamp test
- the participants' within- and between-day glycemic variability as determined by seven point selfmonitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) during 5 days preceding each clamp procedure
- perform oral glucose tolerance tests (OGTTs; only in relatives), determine HbA1c levels centrally (relatives and patients) and record insulin requirements and hypoglycemic episodes (in patients) Our previous experiments have documented that the selected patients and relatives (see workplan) display large inter-individual differences in functional beta cell mass (ranging anywhere between control values and < 10% of controls) allowing to study glycemic variability as a function of residual cell function over a large range of values. They also illustrate that the recruitment capacity of the clinical network and the acceptance rate and compliance of the patients and relatives for the clamp procedure is high and sufficient to carry out the planned experiments.
- Conditions
- Type 1 Diabetes
- Being tested
- Glucose, Continuous glucose monitoring
- Keywords
- type 1 diabetes, Prevention, First degree relatives, High risk for type 1 diabetes
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucoseDrug
Also called Stimulated glucose
Glucose 20% intravenous
Continuous glucose monitoringDevice
Also called CGM
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Glucose; Device: Continuous glucose monitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (2)
Follow up of OGTT's and HbA1c levels in high risk first degree relatives and patients
- perform oral glucose tolerance tests (OGTTs; only in relatives), determine HbA1c levels centrally (relatives and patients) and record insulin requirements and hypoglycemic episodes (in patients)
Measured: 2 years
evaluate the continuous glucose monitoring to measure within- and between-day glycemic variability
to measure within- and between-day glycemic variability as determined by seven point selfmonitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) during 5 days preceding each clamp procedure
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionJul 2015 (estimated)
- Study completionJul 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Collaborators
- Vrije Universiteit Brussel, University Hospital, Ghent, University Hospital, Antwerp
- Responsible party
- Principal investigator, Bart Keymeulen, Universitair Ziekenhuis Brussel
- Investigators
- Frans K Gorus, MD. PhD., Principal investigator, UZ Brussels
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01402037
- Sponsor's protocol ID
- KD_BF_02
- Status last verified
- Dec 2013
- First submitted
- 7 Jul 2011
- Last updated
- 30 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relation Between Residual Beta Cell Function and Glycemic Variability in (Pre) Type 1 Diabetes.
- ClinicalTrials.gov ID
- NCT01402037
- Acronym / sponsor ID
- KD_BF_02
- Conditions
- Type 1 Diabetes
- Keywords
- type 1 diabetes, Prevention, First degree relatives, High risk for type 1 diabetes
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Collaborators
- Vrije Universiteit Brussel, University Hospital, Ghent, University Hospital, Antwerp
- Study start
- Jul 2011
- Primary completion
- Jul 2015 (estimated)
- Study completion
- Jul 2016 (estimated)
- First posted
- 26 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The established clinical network and the developed dynamic function tests and biological markers provide us with the unique opportunity to identify sufficiently large groups of high-risk first-degree relatives (> 50% risk of diabetes) of a proband with type 1 diabetes and of recent-onset type 1 diabetic patients with the overall aim to investigate the correlation between functional beta cell mass and glycemic variability in relation to metabolic outcome in order to determine thresholds of residual function below which:
- glucose tolerance starts to decline sharply in relatives
- the risk of deteriorating metabolic control and (severe) hypoglycemic events strongly increases in patients
To this effect we will:
- measure and follow over a two-year period
- the functional beta cell mass of participants as determined by AUC C-peptide release - the preferred outcome measure in type 1 diabetes trials during hyperglycemic clamp test
- the participants' within- and between-day glycemic variability as determined by seven point selfmonitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) during 5 days preceding each clamp procedure
- perform oral glucose tolerance tests (OGTTs; only in relatives), determine HbA1c levels centrally (relatives and patients) and record insulin requirements and hypoglycemic episodes (in patients) Our previous experiments have documented that the selected patients and relatives (see workplan) display large inter-individual differences in functional beta cell mass (ranging anywhere between control values and < 10% of controls) allowing to study glycemic variability as a function of residual cell function over a large range of values. They also illustrate that the recruitment capacity of the clinical network and the acceptance rate and compliance of the patients and relatives for the clamp procedure is high and sufficient to carry out the planned experiments.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NDP 12-39 y | Other | Drug: Glucose, Device: Continuous glucose monitoringIn 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 |
| NDP 5-12 y | Other | Device: Continuous glucose monitoringTen 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. |
| FDR 12-39 y | Other | Drug: Glucose, Device: Continuous glucose monitoringIn 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. |
| FDR 5-12 y | Other | Drug: Glucose, Device: Continuous glucose monitoringTen 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. |
Who may qualify
- Ages
- 5 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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)
- aged 12-39 years at inclusion
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlucoseAlso: Stimulated glucoseGlucose 20% intravenous | Drug | FDR 12-39 y, FDR 5-12 y, NDP 12-39 y |
| Continuous glucose monitoringAlso: CGMBlood 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. | Device | FDR 12-39 y, FDR 5-12 y, NDP 12-39 y, NDP 5-12 y |
Primary outcome
evaluate the hyperglycemic clamp to measure the functional beta cell mass test
Time frame: 2 years
to measure the functional beta cell mass of participants as determined by AUC C-peptide release during hyperglycemic clamp test
2 secondary outcomes
Follow up of OGTT's and HbA1c levels in high risk first degree relatives and patients
Time frame: 2 years
evaluate the continuous glucose monitoring to measure within- and between-day glycemic variability
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frans K Gorus, MD PhD contact
Frans K Gorus, MD. PhD. principal investigator
UZ Brussels
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glucose and Continuous glucose monitoring in people with Type 1 Diabetes, run by Universitair Ziekenhuis Brussel at 3 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Frans K Gorus, MD PhD (+32 2 477 50 31), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
evaluate the hyperglycemic clamp to measure the functional beta cell mass test (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2013.