Prevention of Clinical Onset of Type 1 Diabetes in High Risk First Degree Relatives

NCT ID: NCT00654121

Last Updated: 2008-04-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-02-29

Study Completion Date

2007-11-30

Brief Summary

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Prophylactic administration of metabolically active insulin can prevent or delay clinical onset of diabetes in a high risk group of nondiabetic siblings as defined by positivity for autoantibodies against IA-2 (IA-2-A).

Detailed Description

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Hypotheses:

Primary: Prophylactic administration of metabolically active insulin can prevent or delay clinical onset of diabetes in a high risk group of nondiabetic siblings as defined by positivity for autoantibodies against IA-2 (IA-2-A).

Secondary: 1) Untreated siblings with positivity for IA-2-A develop clinical diabetes significantly faster than untreated offspring with the same marker positivity. 2) Plasma proinsulin levels increase disproportionately before clinical onset of Type 1 diabetes both in siblings and offspring. 3) Prophylactic administration of metabolically active insulin reduces the plasma proinsulin/C-peptide ratio in non-diabetic antibody positive siblings and offspring. 4) Prophylactic administration of metabolically active insulin reduces the presence and/or levels of diabetes-associated autoantibodies directed against islet cell components.

Endpoints: Fasting glycemia; fasting and stimulated plasma C-peptide and proinsulin values; islet cell autoantibodies; incidence of hypoglycemia; body weight gain.

Conditions

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Diabetes, Type I

Keywords

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prevention

Study Design

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Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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1

56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)

Group Type ACTIVE_COMPARATOR

Actrapid HM

Intervention Type DRUG

56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)

2

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Actrapid HM

56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Sibling/offspring of a Type 1 diabetic patient
* in good general condition
* age 5-39 years
* fasting plasma glucose \<126 mg/dL AND an OGTT that is non-diabetic by 1997 ADA criteria (33):

1. Normal glycemia:

* fasting plasma glucose \< 110 mg/dL and
* 2 hour plasma glucose \< 140 mg/dL
2. Impaired Fasting Glucose (IFG):

* fasting plasma glucose 110-125 mg/dL and
* 2 hour plasma glucose \< 140 mg/dL
3. Impaired Glucose Tolerance (IGT):

* fasting plasma glucose \<110 mg/dL and
* 2 hour plasma glucose 140-199 mg/dL
* at least positive for IA-2-A
* absence of a protective DQ genotype: A4-B2/X or X/Y or X/X where X = A2-B3.3, A1-B1.9, A1-B1.2, A4-B3.1, A2-B2 or A4.23-B3.1 Y = A1-B1.1, A1-B2, A1-B1.AZH, A3-B2, A3-B3.1, A3-B3.3, A3-B4, A4-B4, A4.23-B4, A4-B3.2, A3-B1.1, A4-B3.3, A4-B1.1 or A4.23-B2 (32)
* cooperative and reliable subject (age ≥ 14 yrs) / parents (age \< 14 yrs) giving informed consent by signature; the patient/parents should be informed in sufficient detail on the content and procedure of the protocol, indicating potential risks of insulin therapy; early intervention with metabolically active insulin treatment should be identified as a clinical trial. Both parents should sign and agree with the protocol procedure.

Exclusion Criteria

* diabetes by 1997 ADA criteria (33):

* fasting plasma glucose ≥ 126 mg/dL, or
* 2 hour plasma glucose ≥ 200 mg/dL
* donation of blood during the study or within one month prior to screening
* pregnancy or lactation in women
* use of inadequate anticonception by female patients of childbearing potential
* use of illicit drugs or overconsumption of alcohol (\> 3 beers/day) 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)
* presently participating in another clinical study or having done so during the last 12 months
* history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient
Minimum Eligible Age

5 Years

Maximum Eligible Age

39 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novo Nordisk A/S

INDUSTRY

Sponsor Role collaborator

AZ-VUB

OTHER

Sponsor Role lead

Responsible Party

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Free University Brussels

Principal Investigators

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Frans Gorus, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuis Brussel

Evy Vandemeulebroucke, MD

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuis Brussel

Locations

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Universitair Ziekenhuis Antwerpen

Antwerp, , Belgium

Site Status

Academisch Ziekenhuis and Diabetes Research Center - Brussels Free University-VUB

Brussels, , Belgium

Site Status

Department of Endocrinology and Nephrology, UZ Gasthuisberg, Katholieke Universiteit Leuven -KUL

Leuven, , Belgium

Site Status

Countries

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Belgium

References

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Decochez K, Truyen I, van der Auwera B, Weets I, Vandemeulebroucke E, de Leeuw IH, Keymeulen B, Mathieu C, Rottiers R, Pipeleers DG, Gorus FK; Belgian Diabetes Registry. Combined positivity for HLA DQ2/DQ8 and IA-2 antibodies defines population at high risk of developing type 1 diabetes. Diabetologia. 2005 Apr;48(4):687-94. doi: 10.1007/s00125-005-1702-x. Epub 2005 Mar 9.

Reference Type BACKGROUND
PMID: 15756536 (View on PubMed)

Gorus FK, Weets I, Decochez K, van der Auwera BJ. [Preventative biology of type 1 diabetes: implications for clinical preventative studies]. Verh K Acad Geneeskd Belg. 2003;65(4):203-29; discussion 229-31. Dutch.

Reference Type BACKGROUND
PMID: 14534938 (View on PubMed)

Decochez K, De Leeuw IH, Keymeulen B, Mathieu C, Rottiers R, Weets I, Vandemeulebroucke E, Truyen I, Kaufman L, Schuit FC, Pipeleers DG, Gorus FK; Belgian Diabetes Registry. IA-2 autoantibodies predict impending type I diabetes in siblings of patients. Diabetologia. 2002 Dec;45(12):1658-66. doi: 10.1007/s00125-002-0949-8. Epub 2002 Nov 12.

Reference Type BACKGROUND
PMID: 12488955 (View on PubMed)

Vandemeulebroucke E, Keymeulen B, Decochez K, Weets I, De Block C, Fery F, Van de Velde U, Vermeulen I, De Pauw P, Mathieu C, Pipeleers DG, Gorus FK; Belgian Diabetes Registry. Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients. Diabetologia. 2010 Jan;53(1):36-44. doi: 10.1007/s00125-009-1569-3. Epub 2009 Nov 7.

Reference Type DERIVED
PMID: 19898832 (View on PubMed)

Other Identifiers

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EVDM IT 001

Identifier Type: -

Identifier Source: org_study_id