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

Diabetes, Type I Clinical Trial

Official title:

Prevention of Clinical Onset of Type 1 Diabetes by Daily Administration of Metabolically Active Insulin in High Risk First Degree Relatives.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00654121
• Other study ID #: EVDM IT 001
• Status: Completed
• Phase: Phase 2
• First received: April 2, 2008
• Last updated: April 4, 2008
• Start date: February 2000
• Est. completion date: November 2007

Study information

• Verified date: April 2008
• Source: AZ-VUB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: November 2007
• Est. primary completion date: April 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 5 Years to 39 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes, Type I

Intervention

Drug:
• Actrapid HM
56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Antwerpen
Belgium	Academisch Ziekenhuis and Diabetes Research Center - Brussels Free University-VUB	Brussels
Belgium	Department of Endocrinology and Nephrology, UZ Gasthuisberg, Katholieke Universiteit Leuven -KUL	Leuven

Sponsors (2)

Lead Sponsor	Collaborator
AZ-VUB	Novo Nordisk A/S

Country where clinical trial is conducted

Belgium, 

References & Publications (3)

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. Epub 2002 Nov 12. — View Citation

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. Epub 2005 Mar 9. — View Citation

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. Review. Dutch. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting glycemia;		2004	No
Primary	fasting and stimulated plasma C-peptide and proinsulin values;		2004	No
Primary	islet cell autoantibodies;		2004	No
Primary	body weight gain.		2004	No