Anti-inflammatory Therapy With Anakinra in Newly Diagnosed Type 1 Diabetes

NCT00645840 | Completed Phase 1 Results

• 1 other identifier: UTSW 112007-037
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether control of inflammatory pathways mediated by IL-1 beta using the IL-1 receptor antagonist anakinra will yield measurable decreases in expression of genes that are otherwise overexpressed as a consequence of IL-1 beta effects in children with newly diagnosed type 1 diabetes. Ultimately, we believe that control of IL-1 beta pathways will be associated with preserved insulin secretory capacity.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 diabetes mellitus; IL1 beta; Anakinra

Outcome Measures

Primary Outcomes (1)

• Effect of Anakinra Treatment on PBMC Gene Expression for Patients

  Expression data at baseline and after treatment were available on 10 patients who had received anakinra. These were compared to similarly-timed samples from 10 patients from control group B. Several attempts have been made to contact the PI to verify information, but were unsuccessful. Unable to verify if 10 or 12 patients were analyzed.

  1 month

Secondary Outcomes (1)

• C-peptide Secretory Capacity

  7 months

Study Arms (1)

Anakinra

EXPERIMENTAL

After study enrollment, all subjects started anakinra (Kineret™; Amgen, Thousand Oaks, CA, USA) as a subcutaneous daily injection. Subjects weighing \>25 kg at the time of enrollment received 100 mg daily, whereas those weighing \<25 kg received 50 mg daily. Anakinra was continued for 28 d with no dose adjustment.

Drug: Anakinra

Interventions

Anakinra DRUG

Patients will receive daily anakinra therapy for 28 days

Also known as: Kineret

Anakinra

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Newly diagnosed type 1 diabetes (by ADA criteria) within 1 week of diagnosis.
• Age 6-18 years.
• Males and females will be recruited.
• Subjects and families must be English and/or Spanish-speaking.

You may not qualify if:

• Patients with active bacterial infections must be cured prior to entry into the study protocol.
• Serum creatinine \> 1.5 mg/dL or greater than 1.5x the upper limit of normal for age
• Serum ALT or AST \> 3 times the upper limit of normal for the lab
• Platelet count \< 100,000/mm3
• WBC count \< 3,000 cells/mm3
• Hemoglobin, Hematocrit or Red blood cell count outside 30% of the upper or lower limits of normal for the lab
• Any medication that, in the opinion of the investigator, is being administered for immunomodulatory purposes, including but not limited to systemic or inhaled corticosteroids and chronic NSAIDs
• Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit
• Treatment in the past with anakinra
• Patients with known hypersensitivity to E. coli-derived proteins, anakinra, or any components of anakinra.
• Must not have received immunosuppressive agents (including systemic or inhaled corticosteroids and scheduled/chronic NSAIDs) for at least three months prior to enrollment
• Known HIV-positive status or known history of any other immunodeficiency state.
• Any mycobacterial disease
• Active severe infections within 4 weeks before screening visit, or between the screening and baseline visits.
• Severe comorbidities (congestive heart failure of any severity, myocardial infarction, cerebrovascular accident or transient ischemic attack within 3 months of screening visit, unstable angina pectoris, uncontrolled hypertension (sitting systolic BP \<80 mm Hg or \> 160 or diastolic BP \> 100 mm Hg), oxygen-dependent severe pulmonary disease, history of cancer within 5 years \[other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer\])

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Children's Medical Center Dallas: collaborator

Study Sites (1)

Children's Medical Center

Dallas, Texas, 75235, United States

Location

Related Publications (1)

• Sumpter KM, Adhikari S, Grishman EK, White PC. Preliminary studies related to anti-interleukin-1beta therapy in children with newly diagnosed type 1 diabetes. Pediatr Diabetes. 2011 Nov;12(7):656-67. doi: 10.1111/j.1399-5448.2011.00761.x. Epub 2011 Apr 24.

  PMID: 21518168 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Interleukin 1 Receptor Antagonist Protein

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)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

This pilot study was not designed or powered for any clinical end-point, and the duration of anakinra therapy was brief, limiting the conclusions to be drawn.

Results Point of Contact

• Title: Perrin White
• Organization: UT Southwestern Medical Center

perrin.white@utsouthwestern.edu

214 648 6875

Study Officials

• Soumya Adhikari, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2008
• First Posted: March 28, 2008
• Study Start: March 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: November 14, 2019
• Results First Posted: November 14, 2019

Record last verified: 2019-10

Locations

US (1)