Maintaining Immune and Mitochondrial Functions in Old Adults With SAfe Nutrition: the MIMOSA Study.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 240
- 试验地点
- 2
- 主要终点
- Change in mitochondrial ATP production (nmol/ml)
研究概览
简要总结
Aging is associated with an increased inflammation named "inflammageing" and with an altered immune response. Different mechanisms have been proposed to explain the phenomenon of inflammageing and increased oxidative stress: deficiencies in essential amino acids, and some micronutrients have an important impact and may induce immune cell dysregulation. Mitochondrial dysfunction may explain the complex relationship between malnutrition sarcopenia, immune dysfunction and aging.
Therefore, a personalized nutritional strategy aiming to improve mitochondrial function, decrease oxidative stress, down-regulate inflammation and restore immunity appears to be a logical approach in order to treat malnutrition and its biological and clinical consequences.
MIMOSA will investigate the role of nutritional supplements in rescuing altered mitochondrial function and redox state imbalance.
详细描述
The study participants will all receive optimal standard care ensuring the optimal protein and energy intakes, with at least 1 g protein per kg body weight and day, and 30 kcal per kg body weight and day (or the measured energy expenditure (EE) value). This will be realized by the daily administration of oral nutritional supplements (ONS) providing whole proteins together with dietary advice [according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, Nestlé) and nutritional counselling (SC).
All participants included in this study will receive daily, the oral nutritional supplement (ONS), one sachet and two capsule (for blinding purpose).
The intervention nutrients will be delivered as follows:
- BCAA: 1 sachet containing 4 g of BCAA (details in Table 1)
- Micronutrients: 1 sachet containing 4 g of the micronutrient blend and 2 capsules containing 0.6 g of OMEGA 3 PUFA (details in table 1).
The placebos will be delivered like this:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The intervention nutrients will be delivered as powder in sachets identified as B (BCAA, 4 gr) or C (mixture of micronutrients, 4 gr), placebo sachets identified as A will contain maltodextrin, (4 gr); the sachets will be mixed by the patients in a juice. Blinding will be maintained until interim evaluation and after for the full trial. In order to assure the blinding the sachets will be opaque identified by a single letter ready to be mixture with a juice with similar taste and texture between the different formulations
入排标准
- 年龄范围
- 75 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥75 years
- •Patients entering a rehabilitation program
- •Diagnosis of malnutrition defined by a MNA-SF (mini-nutritional assessment short form) score below 11 points.
- •Commitment to accept the nutritional supplement proposed, willing and able to give written informed consent
- •Ability to understand and comply with the requirements of the study
排除标准
- •Presence of malignancy,
- •Life expectancy of less than two months calculated by Multidimensional Prognostic Index (MPI ),
- •Congestive heart failure (NYHA IV),
- •Chronic renal disease (creatinine clearance <40 ml/min calculated by cockroft),
- •Liver cirrhosis (Child B-C),
- •Tube/percutaneous endoscopic gastrostomy feeding or parenteral nutrition,
- •Severe dysphagia,
- •Mini-Mental State Examination (MMSE)≤18 and MNA>11 points. MMSE ≥ 18 identifies patients with mild form of cognitive impairment; those patients generally do not have problems in swallowing and are able to take drugs.
- •Severe anaemia (Hb<10 g/l) or leukopenia (<2G/l).
研究组 & 干预措施
Standard treatment (SC)
nutritional counselling (SC) + Placebo: These patients will receive Oral Nutrient Supplementation (ONS) and maltodextrin 4 g
干预措施: standard treatment + placebo (Dietary Supplement)
Micronutrients
In addition to the ONS the patients will receive a combination of micronutrients and PUFA
干预措施: Micronutriments (Dietary Supplement)
结局指标
主要结局
Change in mitochondrial ATP production (nmol/ml)
时间窗: change vesus baseline at 30, 60 days after discharge
Production of ATP will be measured using the ATP Bioluminescent Assay Kit
Change in mitochondrial electron flux (nmol cit/min/mg prot)
时间窗: change vesus baseline at 30, 60 days after discharge
The activity of Complex I and III will be measured on non-sonicated mitochondrial samples
Change in redox state (plasmatic concentration of metabolites)
时间窗: change vesus baseline at 30, 60 days after discharge
analyses of thiometabolome contains: methionine, methionine sulfone, methionine sulfoxide, cysteine, homocysteine, homocystine, cystathionine, formylmethionine, cystine, glutathione, glutathione disulfide, taurine, S-adenosylmethionine, S-adenosylhomocysteine, N-acetylcysteine, cysteic acid, serine, glycine, glutamic acid, lypoic acid, selenocysteine, thioctic acid, pyruvic acid.
次要结局
- change phase angle (score)(change versus baseline at rehab discarge (21 days), 30, 60 days after discharge)
- change in perceived health status (score)(change versus baseline at rehab discarge (21 days), 30, 60 days after discharge)
- change in inflammation(change versus baseline at 30, 60 days after discharge)
- muscle function (score)(change versus baseline at rehab discarge (21 days), 30, 60 days after discharge)
- muscle mass (Kg/body weight)(change versus baseline at rehab discarge (21 days), 30, 60 days after discharge)
- muscle strength (Kg)(change versus baseline at rehab discarge (21 days), 30, 60 days after discharge)
- change micronutrients status (concentration of micronutrients)(change versus baseline at 60 days after discharge)
研究者
Patrizia D'Amelio
associated professor
Centre Hospitalier Universitaire Vaudois