A Phase I/II, 3-Arm, Open Label, Single Centre Study to Investigate the Safety and Effect of Oral GABA Therapy on Beta-Cell Regeneration in Type 1-diabetes Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Adverse events possibly or probably related to GABA treatment
研究概览
简要总结
The main goal of this study is to find a reasonably safe and tolerable treatment for adult patients with type 1-diabetes and that regain some of the endogenous insulin secretion, improve the patients' quality of life (QoL) and reduce the risk of both short- and long-term complications. The hypothesis tested is that oral GABA treatment with the newly developed compound Remygen will be safe and induce regain of some endogenous insulin secretion in adult patients with type 1-diabetes diagnosis for more than five years. The first part of the study will include 6 patients and be performed as a Safety and Dose Escalation study in three steps. The main study is a three-arm, open label, single center, clinical trial. Eligible patients will be randomized into one of three active treatment arms to receive oral GABA treatment for 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent given by patients according to national regulations
- •Type 1 diabetes diagnosed ≥ 5 years at the time of screening
- •Must have been diagnosed with Type 1-diabetes before the age of 25
- •Age ≥18 and ≤50
- •Fasting c-peptide levels should be in the range from not detectable levels up to <0.12 nmol/L
- •For males of childbearing potential adequate contraception is as follows:
- •condom (male)
- •abstinence from heterosexual intercourse
- •female partner using contraception as below listed:
- •oral (except low-dose gestagen (lynestrenol and norethisterone)), 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
排除标准
- •Females of child-bearing potential
- •Previous or current treatment with immunosuppressant therapy (although topical and inhalation steroids are accepted)
- •Treatment with any oral or injected anti-diabetic medications other than insulin
- •Patients on medications which may disturb GABA action, such as Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
- •HbA1c > 90 mmol/mol
- •eGFR <60 ml/min
- •Increased plasma concentrations of alanine aminotransferase (>0.75 μkatl/l for females or >1.1 μkat/l for males) and/or aspartate aminotransferase (>0.60 μkat/l for females or >0.75μkat/l for males).
- •Known cancer disease
- •Known sleeping apnea or pulmonary disorder with carbon dioxide rentention in blood
- •Previous history of pancreatitis or other exocrine pancreatic disorder
- •A history of epilepsy, myasthenia gravis, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
- •A history of alcohol or drug abuse
- •A significant illness other than diabetes within 2 weeks prior to first dosing
- •Known human immunodeficiency virus (HIV) or hepatitis
- •Females who are breastfeeding
- •Males not willing to use adequate contraception during the study period.
- •Known hypersensitivity agains benzodiazepins or any excipients of study drugs
- •Participation in other clinical trials with a new chemical entity within 3 months or 5 half-lives of the new chemical entity, whatever longest.
- •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 or other reasons that, at the investigator's discretion, could affect the subject's current clinical condition during study procedures.
研究组 & 干预措施
Low dose gamma-aminobutyric acid (GABA)
Oral GABA treatment 200 mg daily for 6 months
干预措施: Gamma-Aminobutyric Acid (GABA) (Drug)
High dose gamma-aminobutyric acid (GABA)
Oral GABA treatment 600 mg daily for 6 months
干预措施: Gamma-Aminobutyric Acid (GABA) (Drug)
High dose gamma-aminobutyric acid (GABA) + Alprazolam
Oral Alprazolam treatment 0.5 mg daily combined with oral GABA treatment 600 mg daily for 3 months. Alprazolam treatment thereafter ended, and study subjects will continue with oral GABA treatment 600 mg daily only for another 3 months.
干预措施: Gamma-Aminobutyric Acid (GABA) (Drug)
High dose gamma-aminobutyric acid (GABA) + Alprazolam
Oral Alprazolam treatment 0.5 mg daily combined with oral GABA treatment 600 mg daily for 3 months. Alprazolam treatment thereafter ended, and study subjects will continue with oral GABA treatment 600 mg daily only for another 3 months.
干预措施: Alprazolam (Drug)
结局指标
主要结局
Adverse events possibly or probably related to GABA treatment
时间窗: 6 months
To evaluate the acute and long-term safety of oral GABA treatment. The endpoint will investigate number of adverse events possibly or probably related to GABA treatment.
次要结局
- Change in exogenous insulin consumption by treatment(7 months)
- Change in variables that indicate effects on immune system(7 months)
- Change in diabetes treatment satisfaction questionnaire(7 months)
- Difference in C-peptide response to mixed meal tolerance test before and directly after treatment(6 months)
- Difference in glucagon response during a hypoglycemic clamp before and after treatment(7 months)
- Change in HbA1c by treatment(7 months)
- Change in fasting C-peptide by treatment(7 months)
- Difference in C-peptide response to mixed meal tolerance test during and after treatment(7 months)
- Difference in maximum stimulated C-peptide to mixed meal tolerance test during and after treatment(7 months)
- Difference in C-peptide response to mixed meal tolerance test during and after treatment between treatment groups(7 months)
- Difference in glucagon response during a hypoglycemic clamp between treatment groups before and after treatment(7 months)
- Change in GABA plasma levels(7 months)
研究者
Per-Ola Carlsson
Professor, Senior consultant
Uppsala University Hospital