Multicentric Trial on the Use of Combined Therapy of Thiamine and Biotine in Patients With Huntington´s Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 3
- 主要终点
- Incidence of Treatment-Emergent Adverse Events as assessed by clinical examination anamnesis and Analytical monitoring with hematological and biochemical control (hepatic and renal function)
研究概览
简要总结
Evaluate the safety and tolerability of combined oral thiamine with biotin therapy in patients with Huntington´s disease in mild to moderate stages and it is intended to evaluate the biological effect of the treatment in the central nervous system of these patients using as the main biomarker the increase in the level of thiamine monophosphate (TMP) in cerebrospinal fluid (CSF) of these patients with Huntington Disease (HD) during a follow-up period of one year.
Our main hypothesis is that combined thiamine-biotin oral therapy is a secure and well-tolerated treatment, potentially capable of modifying the disease course or avoiding the progression of symptoms in early-stages HD patients
详细描述
The assessment of the safety and tolerability of the combined oral thiamine and biotin therapy in patients with HD will be performed by:
- Periodic clinical examination and anamnesis directed by a neurologist during face-to-face and non-contact visits.
- The collection of adverse effects during interviews of face-to-face visits to assess tolerability.
- Analytical monitoring with hematological and biochemical control (hepatic and renal function) during the dose escalation period, subsequently being this periodic control every 3 months, from signature of informed consent until the end the follow up.
The evaluation of the biological efficacy of treatment with combined oral thiamine and biotin therapy in increasing thiamine monophosphate (TMP) levels in cerebrospinal fluid (CSF) of patients with HD is to be performed by:
- The determination of thiamine levels: free thiamine, TMP, and thiamine pyrophosphate (TTP) in CSF and blood of patients at the beginning and after the end of the study.
- Comparison of thiamine levels (free, TMP and TTP) between the start and the end of the study in CSF and serum of patients with HD.
The evaluation of the biological efficacy of the treatment with combined oral thiamine and oral biotin therapy in neurodegeneration produced in HD will be performed by:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of legal age with manifest Huntington's disease with motor symptoms (chorea, dystonia or bradykinesia) and/or neuropsychiatric; and genetic confirmation of a number of repetitions of the cytosine-adenine-guanine trinucleotide (CAG triplet) in the HTT gene (coding for HTT) greater than or equal to 39
- •Patients should be capable of giving informed consent and attending the planned visit of the study.
- •Women of childbearing age should obtain a negative result in the serum or urine pregnancy test at the screening visit. They must also accept the use of appropriate contraceptive methods during the course of the clinical trial and men who have a partner of childbearing age, accept the use of contraceptive methods
排除标准
- •Medical comorbidities considered clinically significant by the clinical judgment of the investigators.
- •Pregnancy or lactation
- •Patients with HD dependents on the basic routine daily life activities (UHDRS TFC < 7) or a severe cognitive decline.
- •Active psychosis at the moment of the screening evaluation.
- •Severe renal failure.
- •Patients previously treated with thiamine and/or biotin or enrolled in other HD clinical trial with oligonucleotide antisense (IONIS-HTTRX (RG6042).
研究组 & 干预措施
Moderate doses
moderate doses of combination therapy applying the minimum average dosage of thiamine and biotin used in patients with BTBGD
干预措施: Moderate doses of Thiamine y Biotin (Drug)
High doses
high doses of the combination therapy applying the average standard dosage of thiamine and biotin used in patients with BTBGD.
干预措施: High doses of Thiamine y Biotin (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events as assessed by clinical examination anamnesis and Analytical monitoring with hematological and biochemical control (hepatic and renal function)
时间窗: From signature of informed consent form, at all scheduled visits, to end of follow up week 52
Patient´s condition and emergence of comorbidity by clinical examination and anamnesis directed by a neurologist, by measuring of vital signs (blood pressure, heart rate,breath rate weight and height)
次要结局
- The evaluation of the efficacy of treatment with combined oral thiamine and biotin therapy in increasing thiamine monophosphate (TMP) levels in CSF of patients with HD(At baseline (week 0) and visit 8 (week 48))