The Effects Of Casein Glycomacropeptide On Metabolic Control And General Health Status In Children And Adults With PKU: A Randomised Crossover Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Change in overnight fasting plasma Phe
研究概览
简要总结
Randomised controlled trial with a crossover design. For early and continuously treated patients with phenylketonuria (PKU) that are adherent. Two 12-week periods where patients consume either casein glycomacropeptide (CGMP) based protein substitute or a free amino acid (AA) based protein substitute. 4 week wash out period in between. The protein substitutes will be consumed daily together with the patient's regular low protein diet.
详细描述
The study is a randomised controlled trial with a crossover design conducted at several international study centres.
The study population is early and continuously treated patients with PKU that are adhering to their prescribed diet.
The participants will be given both a CGMP based protein substitute and a free AA based protein substitute as their main protein source on two different 12-week periods in a crossover design. The two periods will be separated by a 4 week wash out period.
The protein substitutes will be consumed daily together with the patient's regular low protein diet during the intervention periods.
Primary Objective The primary objective of the study is to investigate the effects of a CGMP based formula compared to an AA based formula upon mean plasma Phe levels after 12 weeks of daily intake in patients with PKU.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PKU patient diagnosed on newborn screening (NBS).
- •> 50% of protein intake from protein substitutes.
- •(CHILDREN) Dietary intake of ≤ 1000 mg Phe from natural protein or ≤20 g natural protein inclusive of fruit and vegetables per day.
- •(ADULTS) Dietary intake of ≤ 1500 mg Phe from natural protein or ≤ 30 g natural protein inclusive of fruit and vegetables per day.
- •(CHILDREN) Three out of the last four consecutive Phe measurements within the target range (≤360 µmol/L in patients aged 4-12 years).
- •(ADULTS) Two out of the last four consecutive Phe measurements within the target range (≤600 µmol/L for adults).
- •Male or female aged 4-12 years or 18 years and over.
- •Early and continuously treated. Adherent to their prescribed PKU diet consisting of a protein-restricted diet and free AA based protein substitute.
- •Otherwise in good general health as evidenced by medical history.
- •Able to provide written informed consent (patient or parent/guardian).
- •Able to comply with the study protocol and take study product according to the opinion of the PI.
- •Protein substitute intake provided by L-amino acid supplements only.
- •(ADULTS) No studies have been done in pregnant women. To ensure patients safety, female patients of childbearing potential must have a negative pregnancy test prior to completing the screening procedures.
- •(ADULTS) All female patients of childbearing potential and sexually mature males should be willing to use a medically accepted method of contraception throughout the study.
- •Successful 3-day PKU Sphere taste test.
排除标准
- •Concomitant diseases / disorders such as but not limited to renal or gut disease / disorders and diabetes.
- •Currently or previously treated with tetrahydrobiopterin (BH4), pegylated recombinant phenylalanine ammonia lyase (PEG PAL), large neutral amino acids.
- •Previous intake of CGMP for more than four consecutive weeks.
- •Having a current infection.
- •Known soya, milk or fish allergies / intolerance.
- •Patients who are currently participating in, plan to participate in, or have participated in an interventional investigational drug, food or medical device trial within 30 days prior to screening visit.
- •Where applicable, patients not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force.
研究组 & 干预措施
L-amino Acids
The specific amount and timing of L-amino acid consumption will be at the instruction of a dietitian following a review of the individual patient's dietary needs.
Consumption period: 12 weeks.
干预措施: L-amino acid protein substitute (Dietary Supplement)
PKU Sphere
The specific amount and timing of PKU sphere consumption will be at the instruction of a dietitian following a review of the individual patient's dietary needs.
Consumption period: 12 weeks.
干预措施: CGMP protein substitute (Dietary Supplement)
结局指标
主要结局
Change in overnight fasting plasma Phe
时间窗: Measured at days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5)
Overnight fasting plasma phenylalanine level (μmol/l)
Change in overnight fasting plasma Tyr
时间窗: Measured at days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5)
Overnight fasting plasma tyrosine level (μmol/l)
Change in overnight fasting blood Phe
时间窗: Measured twice per week up to 32 weeks
Overnight fasting blood phenylalanine level (μmol/l) using blood spots
Change in overnight fasting blood Tyr
时间窗: Measured twice per week up to 32 weeks
Overnight fasting blood tyrosine level (μmol/l) using blood spots
次要结局
- Change in gut health: Stool pH for reducing sugars(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in gut health: Short chain fatty acids(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in anthropometric measurements: weight(Days -31 (visit 1), 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in gut health: PedsQL Gastrointestinal Symptoms Scales, Version 3.0(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in gut health: Stool calprotectin(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in gut health: Immunoglobulin A(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in gut health: 3 day weighed diet diary(Completed for 3 days prior to days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in anthropometric measurements: height(Days -31 (visit 1), 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Glucose(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in cystine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in gut health: Bristol stool form scale(Completed for 7 days prior to days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Albumin(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Pre-albumin(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Transferrin(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Retinol-binding protein(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Haemoglobin A1C(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in IGF-1(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in C-peptide(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in asparagine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Short chain fatty acids(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in arginine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in glutamate(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in isoleucine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in ornithine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in serine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change insulin production(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in alanine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in citrulline(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in glycine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in glutamine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in histidine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in threonine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in tryptophan(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in tyrosine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in renal biomarkers: Serum creatinine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in leucine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in lysine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in methionine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in proline(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in phenylalanine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in taurine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in valine(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in renal biomarkers: Serum cystatin C(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in renal biomarkers: Blood urea nitrogen(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in C-reactive protein (high sensitivity measurement)(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Serum myeloid-related protein(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Inflammatory cytokine panel(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in oxidative stress:Total antioxidant reactivity (TAR)(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Adiponectin(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in Soluble Interleukin 2 Receptor(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in oxidative stress: White cells glutathione (GSH)(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in oxidative stress: Plasma thiobarbituric acid-reactive species (TBAR)(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).)
- Change in patient opinion of acceptability of the product(Days 84 (visit 3) and 196 (visit 5))
- Change in hunger(Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5))