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Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.

ABSTRACT: To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe.We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria.This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15-49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained.The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA-MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean ± SE increase in plasma Phe (62 ± 40 ?mol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 ± 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (-85 ± 40 ?mol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 ± 34 ?mol/L, GMP-MFs = 497 ± 34 ?mol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different.GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP-MFs than with AA-MFs may enhance dietary adherence for individuals with phenylketonuria. This trial was registered at www.clinicaltrials.gov as NCT01428258.

SUBMITTER: Ney DM

PROVIDER: S-EPMC4962165 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.

Ney Denise M DM Stroup Bridget M BM Clayton Murray K MK Murali Sangita G SG Rice Gregory M GM Rohr Frances F Levy Harvey L HL

The American journal of clinical nutrition 20160713 2

<h4>Background</h4>To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe.<h4>Objective</h4>We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs p ...[more]

PMID: 27413125

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Project description:BackgroundPhenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine metabolism. The inability to convert phenylalanine (Phe) into tyrosine causes Phe to accumulate in the body. Adherence to a protein restricted diet, resulting in reduced Phe levels, is essential to prevent cognitive decline. Frequent evaluation of plasma Phe levels and, if necessary, adjustment of the diet are the mainstay of treatment. We aimed to assess whether increased self-management of PKU patients and/or their parents is feasible and safe, by providing direct online access to blood Phe values without immediate professional guidance.MethodsThirty-eight patients aged ≥ 1 year participated in a 10 month randomized controlled trial. Patients were randomized into a study group (1) or a control group (2). Group 2 continued the usual procedure: a phone call or e-mail by a dietician in case of a deviant Phe value. Group 1 was given a personal "My PKU" web page with a graph of their recent and previous Phe values, online general information about the dietary treatment and the Dutch PKU follow-up guidelines, and a message-box to contact their dietician if necessary. Phe values were provided on "My PKU" without advice. Outcome measures were: differences in mean Phe value, percentage of values above the recommended range and Phe sample frequency, between a 10-month pre-study period and the study period in each group, and between the groups in both periods. Furthermore we assessed satisfaction of patients and/or parents with the 'My PKU' procedure of online availability.ResultsThere were no significant differences in mean Phe value, percentage of values above recommended range or in frequency of blood spot sampling for Phe determination between the pre-study period and the study period in each group, nor between the 2 groups during the periods. All patients and/or parents expressed a high level of satisfaction with the new way of disease management.ConclusionsIncreased self-management in PKU by providing patients and/or parents their Phe values without advice is feasible and safe and is highly appreciated.Trial registrationThe trial was registered with The Netherlands National Trial Register (NTR #1171) before recruitment of patients.

Project description:Fruits and vegetables containing phenylalanine ≤ 75 mg/100 g (except potatoes) have little impact on blood phenylalanine in phenylketonuria (PKU). In a randomized, controlled, crossover intervention trial, we examined the effect of increasing phenylalanine intake from fruits and vegetables, containing phenylalanine 76−100 mg /100 g, compared with milk protein sources on blood phenylalanine control. This was a five-phase study (4 weeks each phase). In Phase A, patients remained on their usual diet and then were randomly allocated to start Phase B and C (an additional phenylalanine intake of 50 mg/day, then 100 mg from fruits and vegetables containing phenylalanine 76−100 mg/100 g) or Phase D and E (an additional phenylalanine intake of 50 mg/day then 100 mg/day from milk sources). There was a 7-day washout with the usual phenylalanine-restricted diet between Phase B/C and D/E. Blood phenylalanine was measured on the last 3 days of each week. If four out of six consecutive blood phenylalanine levels were >360 μmol/L in one arm, this intervention was stopped. Sixteen patients (median age 10.5 y; range 6−12 y) were recruited. At baseline, a median of 6 g/day (range: 3−25) natural protein and 60 g/day (range: 60−80) protein equivalent from protein substitute were prescribed. Median phenylalanine levels were: Phase A—240 μmol/L; Phase B—260 μmol/L; Phase C—280 μmol/L; Phase D—270 μmol/L and Phase E—280 μmol/L. All patients tolerated an extra 50 mg/day of phenylalanine from fruit and vegetables, containing phenylalanine 76−100 mg/100 g, but only 11/16 (69%) tolerated an additional 100 mg /day. With milk protein, only 8/16 (50%) tolerated an extra 50 mg/day and only 5/16 (31%) tolerated an additional 100 mg/day of phenylalanine. Tolerance was defined as maintaining consistent blood phenylalanine levels < 360 μmol/L throughout each study arm. There was a trend that vegetable protein had less impact on blood phenylalanine control than milk protein, but overall, the differences were not statistically significant (p = 0.152). This evidence supports the PKU European Guidelines cutoff that fruit and vegetables containing 76−100 mg phenylalanine/100 g should be calculated as part of the phenylalanine exchange system. Tolerance of the ‘free use’ of these fruits and vegetables depends on inter-patient variability but cannot be recommended for all patients with PKU.

Project description:BACKGROUND:The population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood phenylalanine (Phe) levels in adults outside pregnancy is a matter of debate. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional, and neurometabolic parameters of the brain. METHODS:The PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week Phe load on cognition and cerebral parameters in adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, noninferiority trial. PARTICIPANTS:Thirty adult patients with early-treated PKU and 30 healthy controls comparable to patients with regard to age, sex, and educational level will be recruited from the University Hospitals Bern and Zurich, Switzerland. Patients are eligible for the study if they are 18?years of age or older and had PKU diagnosed after a positive newborn screening and were treated with a Phe-restricted diet starting within the first 30?days of life. INTERVENTION:The cross-over intervention consists of 4-week oral Phe or placebo administration in patients with PKU. The study design mimics a Phe-restricted and a Phe-unrestricted diet using a double-blinded, placebo-controlled approach. OBJECTIVES:The primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe level influences cognitive performance (working memory assessed with a n-back task) in adults with early-treated PKU. As a secondary objective, the PICO Study will elucidate the cerebral (fMRI, neural activation during a n-back task; rsfMRI, functional connectivity at rest; DTI, white matter integrity; and ASL, cerebral blood flow) and neurometabolic mechanisms (cerebral Phe level) that accompany changes in Phe concentration. Cognition, and structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls. All assessments will take place at the University Hospital Bern, Switzerland. RANDOMIZATION:Central randomization will be used to assign participants to the different treatment arms with age, sex, and center serving as the stratification factors. Randomization lists will be generated by an independent statistician. Blinding: All trial personnel other than the statistician generating the randomization list and the personnel at the facility preparing the interventional product are blinded to the assigned treatment. DISCUSSION:Using a combination of neuropsychological and neuroimaging data, the PICO Study will considerably contribute to improve the currently insufficient level of evidence on how adult patients with early-treated PKU should be managed. TRIAL REGISTRATION:The study is registered at clinicaltrials.gov (NCT03788343) on the 27th of December 2018, at kofam.ch (SNCTP000003117) on the 17th of December 2018, and on the International Clinical Trials Registry Platform of the WHO.

Project description:BackgroundPatients with irritable bowel syndrome (IBS) experience abdominal pain, altered bowel habits, and defecation-related anxiety, which can result in reduced productivity and impaired health-related quality of life (HRQL). Cognitive behavioral therapy (CBT) has been shown to reduce symptoms of IBS and to improve HRQL, but access to qualified therapists is limited. Smartphone-based digital therapeutic interventions have potential to increase access to guided CBT at scale, but require careful study to assess their benefits and risks.ObjectiveThe aim of this study was to test the efficacy of a novel app, Zemedy, as a mobile digital therapeutic that delivers a comprehensive CBT program to individuals with IBS.MethodsThis was a crossover randomized controlled trial. Participants were recruited online and randomly allocated to either immediate treatment (n=62) or waitlist control (n=59) groups. The Zemedy app consists of 8 modules focusing on psychoeducation, relaxation training, exercise, the cognitive model of stress management, applying CBT to IBS symptoms, reducing avoidance through exposure therapy, behavioral experiments, and information about diet. Users interact with a chatbot that presents the information and encourages specific plans, homework, and exercises. The treatment was fully automated, with no therapist involvement or communication. At baseline and after 8 weeks, participants were asked to complete the battery of primary (Irritable Bowel Syndrome Quality of Life [IBS-QOL], Gastrointestinal Symptom Rating Scale [GSRS]) and secondary (Fear of Food Questionnaire [FFQ], Visceral Sensitivity Index [VSI], Gastrointestinal Cognition Questionnaire [GI-COG], Depression Anxiety Stress Scale [DASS], and Patient Health Questionnaire-9 [PHQ-9]) outcome measures. Waitlist controls were then offered the opportunity to crossover to treatment. All participants were assessed once more at 3 months posttreatment.ResultsBoth intention-to-treat and completer analyses at posttreatment revealed significant improvement for the immediate treatment group compared to the waitlist control group on both primary and secondary outcome measures. Gains were generally maintained at 3 months posttreatment. Scores on the GSRS, IBS-QoL, GI-COG, VSI, and FFQ all improved significantly more in the treatment group (F1,79=20.49, P<.001, Cohen d=1.01; F1,79=20.12, P<.001, d=1.25; F1,79=34.71, P<.001, d=1.47; F1,79=18.7, P<.001, d=1.07; and F1,79=12.13, P=.001, d=0.62, respectively). Depression improved significantly as measured by the PHQ-9 (F1,79=10.5, P=.002, d=1.07), and the DASS Depression (F1,79=6.03, P=.02, d=.83) and Stress (F1,79=4.47, P=.04, d=0.65) subscales in the completer analysis but not in the intention-to-treat analysis. The impact of treatment on HRQL was mediated by reductions in catastrophizing and visceral sensitivity.ConclusionsDespite its relatively benign physical profile, IBS can be an extraordinarily debilitating condition. Zemedy is an effective modality to deliver CBT for individuals with IBS, and could increase accessibility of this evidence-based treatment.Trial registrationClinicalTrials.gov NCT04170686; https://www.clinicaltrials.gov/ct2/show/NCT04170686.

Dataset Information

Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.

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Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.

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