Glutathione, Brain Metabolism and Inflammation in Alzheimer's Disease
Ориентир для пациента и семьи
Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: Glycine, N-acetylcysteine, Alanine.
- Кому может быть актуально
- Состояния в реестре: Alzheimer Disease. Базовые параметры: 55 лет — 85 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- США
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Обзор
Alzheimer's disease (AD) is associated with significant, progressive cognitive decline. Key defects in mitochondrial fuel metabolism insulin resistance, inflammation and decreased brain glucose uptake are linked to AD. This trial will investigate the effects of supplementing glycine and N-acetylcysteine vs. alanine as placebo on these defects in AD, and examine the effects on cognition.
Подробное описание
Glutathione (GSH) deficiency, oxidative stress, mitochondrial dysfunction, insulin resistance and inflammation are linked to Alzheimer's disease (AD). In prior studies, investigators have shown that GSH deficiency contributes to mitochondrial impairment and oxidative stress, and that GSH deficiency can be corrected by supplementing its precursors glycine and cysteine (provided as N-acetylcysteine, NAC), with the combination termed GlyNAC.
This randomized clinical trial will evaluate the effect of GlyNAC vs. alanine placebo supplementation provided for 24-weeks to patients with AD, and measure changes in cognition, GSH concentrations, oxidative stress, brain glucose uptake, brain inflammation and insulin resistance.
Participants who are positive for a beta-amyloid PET scan and meeting cognitive screening criteria will be recruited, and enrolled only after meeting eligibility criteria. Before beginning study supplementation they will undergo imaging studies (MRI, FDG-PET and TSPO-PET scans), and only the FDG- and TSPO-PET scans will be repeated after completing 24-weeks of nutrient supplementation. Cognitive measurements, metabolic and mitochondrial measurements (as described below) will be done before supplementation, and after 12-weeks and 24-weeks of completing supplementation.
Вмешательства
- Пищевая добавка Glycine
The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC) - Пищевая добавка N-acetylcysteine
The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC) - Пищевая добавка Alanine
The placebo arm will supplement Alanine
Первичные конечные точки
- Cognition [Срок оценки: Day 0 of supplementation, and 12-weeks and 24-weeks after starting supplementation]
- Brain glucose uptake [Срок оценки: Done before supplementation and 24-weeks after starting supplementation]
- Brain inflammation [Срок оценки: Done before supplementation and 24-weeks after starting supplementation]
Вторичные конечные точки (9)
- Activities of daily living [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Mitochondrial fuel oxidation [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Red-blood cell glutathione, glycine, cysteine and glutamic aid [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Oxidative stress [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Damage due to oxidative stress [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Inflammatory cytokines [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Endothelial dysfunction [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Plasma concentration of Brain-derived neurotropic factor (BDNF) [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
- Mitochondrial energetics [Срок оценки: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation]
Критерии участия
Критерии включения
- Age 55-85 years;
- Gradual and progressive memory loss for more than 1 year, with a Montreal Cognitive Assessment score of 10-20;
- Amyloid positivity on PET scan;
- Availability of a study partner.
Критерии исключения
- hospitalization in past 3 months;
- use of insulin medications;
- untreated thyroid disease;
- creatinine levels >1.5 mg/dL;
- hemoglobin concentration <11.0 g/dL;
- known liver disease, or AST/ALT level >2x ULN;
- history of stroke, brain tumor, active heart failure or active cancer (removable basal cell cancers will not be an exclusion criteria);
- untreated depression or other severe psychiatric disorders;
- pregnancy or nursing (unlikely in this population)
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Рандомизированное
- Модель
- Параллельные группы
- Маскирование
- Тройное слепое
- Основная цель
- Другое
Центры проведения
США · 1 центр
- Baylor College of Medicine — Houston
Идентификаторы
NCT: NCT04740580 · H48186