Trial Outcomes & Findings for Anti-inflammatory Therapy With Anakinra in Newly Diagnosed Type 1 Diabetes (NCT NCT00645840)

Last Updated: 2019-11-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

1 month

Results posted on

2019-11-14

Participant Flow

Participant milestones

Participant milestones
Measure	Anakinra Patients at Children's Medical Center Dallas between ages 6 and 18 yr with type 1 diabetes within 1 wk of diagnosis were eligible. Exclusion criteria included treatment with systemic or inhaled corticosteroids or any other immunomodulatory drug, active infection, history of mycobacterial disease, pregnancy, live vaccine administration within 90 d of enrollment, and severe comorbidities. Patients were excluded if it was uncertain whether they had type 1 or type 2 diabetes.
Overall Study STARTED	15
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Anakinra Patients at Children's Medical Center Dallas between ages 6 and 18 yr with type 1 diabetes within 1 wk of diagnosis were eligible. Exclusion criteria included treatment with systemic or inhaled corticosteroids or any other immunomodulatory drug, active infection, history of mycobacterial disease, pregnancy, live vaccine administration within 90 d of enrollment, and severe comorbidities. Patients were excluded if it was uncertain whether they had type 1 or type 2 diabetes.
Overall Study Protocol Violation	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anakinra n=12 Participants Patients at Children's Medical Center Dallas between ages 6 and 18 years with Type 1 diabetes within one week of diagnosis were eligible. Diabetes care. At diagnosis, all subjects were placed on a basal-bolus insulin regimen with glargine and either lispro or aspart. For the duration of the study, insulin doses were adjusted per standard clinic protocol with target glucose of 80-140 mg/dL fasting and 80-180 mg/dL before meals. At each study visit, we recorded the subject's current insulin doses and weight to allow calculation of the total daily dose (units/kg/day). Anakinra. After study enrollment, all subjects started anakinra (Kineret; Amgen, Thousand Oaks, CA) as a subcutaneous daily injection. Subjects weighing more than 25 kg at the time of enrollment received 100 mg daily whereas those weighing 25 kg or less received 50 mg daily. Anakinra was continued for a total of 28 days with no dose adjustment.
Age, Continuous	12.3 years STANDARD_DEVIATION 2.3 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
A1c (Median (IQR))	11.5 percent n=5 Participants
Beta hydroxybutyrate (mg/dL) (Median (IQR))	6.3 mg/dL n=5 Participants
Total daily insulin dose at hospital discharge (U/kg/day) (Mean)	0.75 Units/kg/day STANDARD_DEVIATION 0.11 • n=5 Participants
Initial IDAA1c (Median (IQR))	14.4 percent n=5 Participants

PRIMARY outcome

Timeframe: 1 month

Population: We enrolled 15 subjects to receive anakinra. Of these subjects, three were later found to have negative autoantibodies and were excluded from further analyses. One subject withdrew from participation and stopped anakinra after two doses. We stopped study drug for another subject after 19 days of therapy due to an adverse event.

Outcome measures

Outcome measures
Measure	Anakinra n=335 probe sets 12 autoantibody positive subjects with newly diagnosed type 1 diabetes who were treated with anakinra
Effect of Anakinra Treatment on PBMC Gene Expression for Patients	0 probe sets

SECONDARY outcome

Timeframe: 7 months

Population: 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.

Mixed-meal tolerance tests. MMTTs were conducted at the UT Southwestern Clinical Translational Research Center (CTRC). Subjects underwent MMTTs at 3-4 wk after diagnosis and again at 7 months after diagnosis. C-peptide analyses were performed by Dr Philip Raskin (UTSouthwestern MedicalCenter, Dallas, TX,USA). C-peptide AUC was calculated for each MMTT using the trapezoidal method. C-peptide AUC data between groups were rank transformed and then analyzed using a two-way repeated measures analysis of variance (ANOVA).

Outcome measures

Outcome measures
Measure	Anakinra n=12 Participants 12 autoantibody positive subjects with newly diagnosed type 1 diabetes who were treated with anakinra
C-peptide Secretory Capacity	160.5 ng/mL/2h Interval 90.8 to 225.0

Adverse Events

Anakinra

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Anakinra n=12 participants at risk Patients at Children's Medical Center Dallas between ages 6 and 18 yr with type 1 diabetes within 1 wk of diagnosis were eligible. Exclusion criteria included treatment with systemic or inhaled corticosteroids or any other immunomodulatory drug, active infection, history of mycobacterial disease, pregnancy, live vaccine administration within 90 d of enrollment, and severe comorbidities. Patients were excluded if it was uncertain whether they had type 1 or type 2 diabetes.
Blood and lymphatic system disorders Lymphadenopathy	8.3% 1/12 • Number of events 12

Other adverse events

Other adverse events
Measure	Anakinra n=12 participants at risk Patients at Children's Medical Center Dallas between ages 6 and 18 yr with type 1 diabetes within 1 wk of diagnosis were eligible. Exclusion criteria included treatment with systemic or inhaled corticosteroids or any other immunomodulatory drug, active infection, history of mycobacterial disease, pregnancy, live vaccine administration within 90 d of enrollment, and severe comorbidities. Patients were excluded if it was uncertain whether they had type 1 or type 2 diabetes.
Skin and subcutaneous tissue disorders Injection site pain	100.0% 12/12 • Number of events 12
Skin and subcutaneous tissue disorders Injection site reaction	91.7% 11/12 • Number of events 11

Additional Information

Perrin White

UT Southwestern Medical Center

Phone: 214 648 6875

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place