A Pilot Study on Safety, Feasibility and Insulin-promotion by Intra-inguinal Lymph Node Injections of Glutamic Acid Decarboxylase (GAD) in Patients With LADA Type of Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Injection Site Skin Reactions
研究概览
简要总结
This study will evaluate the effects of 3 intra-nodal injections of GAD-alum (Diamyd), together with oral vitamin D supplementation. Safety and feasibility of the treatment will be evaluated and also effects on the immune system and on the preservation of endogenous insulin production.
详细描述
The purpose of the trial is to evaluate the effects of 3 intra-nodal injections of GAD-alum, together with oral vitamin D supplementation, in a population of LADA patients with high GADA titers. Effects will be summarized at 5 and 12 months after the first injection.
- The primary objective is to evaluate safety and feasibility of this treatment regimen.
- Secondary objectives are to test if the treatment induces a strong GAD-specific immune response similar to what has previously been observed in type 1 diabetes patients and to test for indications of preservation of endogenous insulin production.
The study is an open label Phase IIa feasibility trial. It is a pilot study that does not include a placebo arm.
Antidiabetic medication in the form of metformin is acceptable before and during the trial. Study participants must be insulin independent at baseline, but if the need for insulin treatment develops during the trial, such treatment will be given.
GAD-alum will be injected directly into an inguinal lymph node by a qualified radiologist.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent by the patient.
- •Diagnosis of LADA and diabetes debut within the last 18 months before inclusion. LADA should be defined by the criteria of age ≥30 years at the onset of diabetes, anti-GAD positivity and no clinical need for permanent insulin treatment during the first 3 months after the diagnosis of diabetes.
- •Fasting C-peptid levels ≥ 0.3 nmol/l
- •High GADA titers (>190 U/ml)
- •Patients must be insulin independent at baseline by clinical judgement and C-peptide criteria
- •Antidiabetic medication in the form of metformin is acceptable for inclusion as well as medications not mentioned under exclusion criteria
- •Females must agree to avoid pregnancy, and must have a negative urine pregnancy test.
- •Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of GAD-alum. Adequate contraception is as follows:
- •For females of childbearing potential:
- •oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives
- •combined (estrogen and progestogen containing)
- •oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
- •intrauterine device
- •intrauterine hormone-releasing system (for example, progestin-releasing coil)
- •bilateral tubal occlusion
- •vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
- •male partner using condom
- •abstinence from heterosexual intercourse
- •For males of childbearing potential:
- •condom (male)
- •abstinence from heterosexual intercourse
排除标准
- •Current or previous treatment with immunosuppressant therapy (topical or inhaled steroids are accepted)
- •Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
- •Systemic treatment with glucocorticoids
- •Treatment with any vaccine, including influenza vaccine, within 1 month prior to planned first study drug dose or planned treatment with any vaccine up to 1 month after the last injection with study drug
- •Antidiabetic medication (metformin excepted)
- •Significantly abnormal hematology results at screening (i.e. anemia with hemoglobin < 12 g/L).
- •A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
- •Clinically significant history of acute reaction to vaccines in the past.
- •Renal disease (as defined by serum creatinine >150 µmol/l)
- •Serious cardiovascular events (myocardial infarction, stroke) within the last year preceding recruitment.
- •Participation in other clinical trials with a new chemical entity within the previous 3 months
- •A history of alcohol or drug abuse
- •Known HIV or hepatitis
- •Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study
- •Other serious chronic disease as judged by investigator.
- •Females who are lactating, are pregnant or intend to become pregnant.
- •Inability or unwillingness to comply with the provisions of this protocol
- •Deemed by the investigator not being able to follow instructions and/or follow the study protocol
- •Treatment any other supplementation of with vitamin D, marketed or not, or unwilling to abstain from such medication during the trial 120 days daily intake of Divisun (non-investigational medicinal product)
研究组 & 干预措施
GAD-vaccination with vitamin D suppletion
Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart.
Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total).
干预措施: recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel (Drug)
GAD-vaccination with vitamin D suppletion
Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart.
Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total).
干预措施: Vitamin D (Drug)
结局指标
主要结局
Injection Site Skin Reactions
时间窗: 1 hour
Injection site skin reactions 1 hour post injection, i.e., erythema, oedema, haematoa, tenderness, pain, itching or other finding.
Occurrence of Adverse Events (AEs) During 5 Months From Baseline.
时间窗: From baseline (first injection of GAD-alum) to 5 months after baseline.
AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized.
Occurrence of Adverse Events (AEs) During the Study.
时间窗: From baseline (first injection of GAD-alum) to 12 months after baseline.
AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit/first injection of GAD-alum). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized.
Serum GAD65A Titers, Change From Baseline at 5 Months After Baseline.
时间窗: Baseline (first injection of GAD-alum) and 5 months after baseline.
Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 5 months after baseline. Calculation: Value at 5 months minus value at baseline.
Serum GAD65A Titers, Change From Baseline at 12 Months After Baseline.
时间窗: Baseline (first injection of GAD-alum) and 12 months after baseline.
Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline.
次要结局
- Insulin Secretion, Change From Baseline to 5 Months After Baseline.(Baseline (first injection of GAD-alum) and 5 months after baseline.)
- Insulin Secretion, Change From Baseline to 12 Months After Baseline.(Baseline (first injection of GAD-alum) and 12 months after baseline.)
- Change in HbA1c(from baseline to 12 months after the first injection)
- Change in Fasting Glucose(From baseline to 12 months after the first injection)
- Change in Fasting C-peptide(Between baseline and 12 months after the first injection)
- Change in Maximum C-peptide During Mixed Meal Tolerance Test (MMTT)(between baseline 12 months after the first injection)