A Phase 3, Randomised, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy, Tolerability, and Safety of Combined Metabolic Activator Supplementation in Subjects Diagnosed With Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 845
- 试验地点
- 8
- 主要终点
- Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score from baseline to end-of-treatment
研究概览
简要总结
This randomised, double-blinded, placebo-controlled study aims to establish metabolic improvements in subjects diagnosed with Alzheimer's Disease (AD) by treatment with CMA2 including N-acetyl-L-cysteine (NAC), L-carnitine-L-tartrate (LCAT), nicotinamide (niacinamide), and L-serine.
Participants will take the drug CMA2 or a placebo twice a day for 26 weeks. They will visit the clinic 4 times for checkups and tests.
详细描述
This will be a randomised, double-blinded, placebo-controlled, multi-centre Phase 3 study with the aim to establish metabolic improvements in subjects diagnosed with AD by dietary supplementation with CMA2, including NAC, LCAT, niacinamide, and L-serine. The study will be performed at approximately 9 clinical sites in Turkey and aims to include a total of 676 evaluable subjects (up to 845 randomised).
The study comprises four clinical visits. Consenting subjects will be screened for eligibility (Visit 1; screening) according to study-specific eligibility criteria within 28 days prior to randomisation and start of IMP administration. Eligible subjects will be randomised on Day 1 (Visit 2) to 26 weeks of b.i.d. oral administration of either CMA2 or placebo (1:1). The first dose will be administered at the study clinic. The subjects will be observed for 2 hours post dose for the development of any allergic reactions or intolerance after taking the first dose. Subjects who cannot tolerate the study agents will be withdrawn from the study.
Visits at the study site will be performed at Week 13 (Visit 5) and Week 26 (Visit 8; end of treatment). Monthly telephone contacts will be scheduled with the patients. At the telephone visits IMP compliance, Concomitant medication and adverse event will be addressed.
The following clinical scales will be used to assess the effect of CMA2 on cognition and daily life activity: MMSE, ADAS-Cog, and ADCS-ADL. Blood samples will be collected for advanced plasma metabolomics, proteomics, and lipidomics analysis. Whole genome sequencing will not be performed.
Optional blood samples will be collected for p- tau217, Nfl, GFAP, and S-Urate analysis. Optional Saliva and faeces sampling for oral and gut microbiome will be collected. CSF samples will be optional collected for determination of Abeta42, total-Tau, p-Tau181 levels and Neurofilament light chain concentrations, and for advanced CSF metabolomics, proteomics, and lipidomics analysis. These samples will be decided by each investigator and will be analysed as exploratory endpoint.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women of non-childbearing potential ≥ 50 years of age.
- •Diagnosed with AD and at the Screening visit having the scores of ADAS-Cog ≥ 12 and GDS≥
- •Stable AD treatments and clinical course for at least 1 month.
- •Females of childbearing potential must have documented tubal ligation or hysterectomy; or be post-menopausal (defined as 12 months of amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 25-140 IE/L and oestradiol <200 pmol/Lis confirmatory]).
- •Able to give written informed consent for participation in the study by the patient and/or legal representatives.
排除标准
- •History of stroke.
- •History of brain trauma < 14 days.
- •Uncontrolled diagnosed depression.
- •Uncontrolled (HbA1C > 8) type 1 or type 2 diabetes.
- •Severe swallowing problems.
- •PEG-feeding.
- •Chronic diarrhoea.
- •Chronic kidney disease with S-Creatinin > 1,30 mg/dl.
- •Active bronchial asthma at the time of screening.
- •History of phenylketonuria (contraindicated for NAC).
- •Known allergy for substances used in the study.
- •Known malignancies.
- •Use of dietary supplements such as vitamins, omega-3 products, or plant stanol/sterol products later than one (1) week prior to inclusion.
- •Use of anti-microbial agents later than one (1) week prior to inclusion.
- •Drug and/or alcohol abuse.
- •Subjects considered as inappropriate for this study for any reason (noncompliance etc.) per investigator assessment.
- •Administration of another new chemical entity (defined as a compound that has not been approved for marketing) or has participated in any other clinical study that included drug treatment with the last administration within 3 months prior to administration of IMP in this study.
研究组 & 干预措施
Treatment Arm
干预措施: Combined metabolic activators (Drug)
Placebo Arm
干预措施: Collagen and maltodextrin (Other)
结局指标
主要结局
Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score from baseline to end-of-treatment
时间窗: Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks)
The test administrator adds up points for the errors in each task for a total score ranging from 0 to 70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment
次要结局
- To evaluate compliance daily two doses treatment in patients(Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in body weight from baseline through-out the study(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in hemoglobin concentration from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in Mini Mental State Examination (MMSE) score from baseline to end-of-treatment(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in blood pressure from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score from baseline to end-of-treatment(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in body height from baseline through-out the study(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in BMI from baseline through-out the study(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in waist and hip circumference from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Changes in liver function tests [Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP)] from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Changes in liver function tests (Total Bilirubin, and Albumin) from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Changes in creatinine kinase (CK) level from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in heart rate from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in red blood cell count from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in platelet count from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in white blood cell count from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Changes in blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Changes in blood glucose levels from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in blood insulin level from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Change in thyroid-stimulating hormone (TSH) level from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))
- Monitoring Adverse Events(26 weeks)
- Changes in kidney function tests from baseline(Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks))