-
Alzheimer's Research & Therapy Feb 2021Brain energy metabolism is impaired in Alzheimer's disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Brain energy metabolism is impaired in Alzheimer's disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients.
METHODS
We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects.
RESULTS
We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild.
CONCLUSIONS
This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia.
TRIAL REGISTRATION
This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.
Topics: Activities of Daily Living; Alzheimer Disease; Cross-Over Studies; Diet, Ketogenic; Humans; Quality of Life
PubMed: 33622392
DOI: 10.1186/s13195-021-00783-x -
Nutrients Nov 2020Non-nutritive artificial sweeteners (NNSs) may have the ability to change the gut microbiota, which could potentially alter glucose metabolism. This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial.
Non-nutritive artificial sweeteners (NNSs) may have the ability to change the gut microbiota, which could potentially alter glucose metabolism. This study aimed to determine the effect of sucralose and aspartame consumption on gut microbiota composition using realistic doses of NNSs. Seventeen healthy participants between the ages of 18 and 45 years who had a body mass index (BMI) of 20-25 were selected. They undertook two 14-day treatment periods separated by a four-week washout period. The sweeteners consumed by each participant consisted of a standardized dose of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose. Faecal samples collected before and after treatments were analysed for microbiome and short-chain fatty acids (SCFAs). There were no differences in the median relative proportions of the most abundant bacterial taxa (family and genus) before and after treatments with both NNSs. The microbiota community structure also did not show any obvious differences. There were no differences in faecal SCFAs following the consumption of the NNSs. These findings suggest that daily repeated consumption of pure aspartame or sucralose in doses reflective of typical high consumption have minimal effect on gut microbiota composition or SCFA production.
Topics: Adolescent; Adult; Analysis of Variance; Aspartame; Biodiversity; Cross-Over Studies; Double-Blind Method; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Microbiome; Health; Humans; Male; Metabolomics; Middle Aged; Non-Nutritive Sweeteners; Phylogeny; Principal Component Analysis; Sucrose; Treatment Outcome; Young Adult
PubMed: 33171964
DOI: 10.3390/nu12113408 -
The American Journal of Clinical... Jun 2020Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on clinical outcomes in RA, but insufficient evidence exists to provide specific dietary advice. Food components may interact but studies evaluating combined effects are lacking.
OBJECTIVES
We aimed to investigate if an anti-inflammatory diet reduces disease activity in patients with RA.
METHODS
In this single-blinded crossover trial, 50 patients with RA were randomly assigned to an intervention diet containing a portfolio of suggested anti-inflammatory foods, or a control diet similar to the general dietary intake in Sweden, for 10 wk. After a 4-mo washout period the participants switched diet. Food equivalent to ∼50% of energy requirements was delivered weekly to their homes. For the remaining meals, they were encouraged to consume the same type of foods as the ones provided during each diet. Primary outcome was change in Disease Activity Score in 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR). Secondary outcomes were changes in the components of DAS28-ESR (tender and swollen joints, ESR, and visual analog scale for general health) and DAS28-C-reactive protein.
RESULTS
In the main analysis, a linear mixed ANCOVA model including the 47 participants completing ≥1 diet period, there was no significant difference in DAS28-ESR between the intervention and control periods (P = 0.116). However, in unadjusted analyses, DAS28-ESR significantly decreased during the intervention period and was significantly lower after the intervention than after the control period in the participants who completed both periods (n = 44; median: 3.05; IQR: 2.41, 3.79 compared with median: 3.27; IQR: 2.69, 4.28; P = 0.04, Wilcoxon's Signed Rank test). No significant differences in the components were observed.
CONCLUSIONS
This trial indicates positive effects of a proposed anti-inflammatory diet on disease activity in patients with RA. Additional studies are required to determine if this diet can cause clinically relevant improvements.This trial was registered at clinicaltrials.gov as NCT02941055.
Topics: Aged; Arthritis, Rheumatoid; C-Reactive Protein; Female; Humans; Male; Middle Aged; Severity of Illness Index; Sweden
PubMed: 32055820
DOI: 10.1093/ajcn/nqaa019 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2022Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms and bowel habits, and to identify possible predictors of clinical response to a low FODMAP diet and FODMAP sensitivity in IBS.
METHODS
Adult participants with IBS (Rome IV criteria, n = 29) were included and adhered to two 7-day diet periods, with either low (4 g/day) or moderate (23 g/day) amounts of FODMAPs, in this randomized, double-blind, crossover study. The periods were separated by a wash-out period (≥14 days). IBS-Severity Scoring System (IBS-SSS) and a stool diary (Bristol Stool Form) were completed before and after the diet periods. At baseline, severity of GI symptoms and gut microbial fermentation were assessed (every 15 min, 4 h) during the Lactulose Nutrient Challenge Test (LNCT). Clinical response and FODMAP sensitivity were defined by reduction after low FODMAP period, and increase after moderate FODMAP period in IBS-SSS (≥50 points), respectively.
RESULTS
Severity of GI symptoms (P = 0.04), stool consistency (P = 0.01), and stool frequency (P = 0.01) differed between the interventions, with reduced overall GI symptom severity, abdominal pain intensity and frequency, bowel habits dissatisfaction, and daily life interference (P < 0.05 for all), as well as more firm (P = 0.03) and less frequent (P < 0.01) stools after low FODMAP intervention, but not after moderate FODMAP intervention. A third (34%) responded clinically to the low FODMAP diet, and the response could be predicted by higher IBS-SSS at baseline (P = 0.02). Although modest associations between FODMAP sensitivity (22%) and GI symptoms during LNCT were observed, no independent predictors could be identified.
CONCLUSIONS
A diet low in FODMAPs reduces GI symptoms and affects bowel habits in IBS, compared with a moderate FODMAP diet. Assessment of IBS severity before the intervention may be used to predict clinical response to a low FODMAP diet. Trial registry (http://www.
CLINICALTRIALS
gov): Registered under Clinical Trial number NCT05182593.
Topics: Adult; Humans; Irritable Bowel Syndrome; Cross-Over Studies; Diet, Carbohydrate-Restricted; Defecation; Lactulose
PubMed: 36384081
DOI: 10.1016/j.clnu.2022.11.001 -
Kidney360 Oct 2021Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia.
METHODS
In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphate 6.0-10.0 mg/dl) and a 1.5 mg/dl increase after phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks of treatment with tenapanor were rerandomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period), and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved ≥1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set.
RESULTS
Of 564 eligible participants randomized to receive tenapanor (=423) or sevelamer carbonate (=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were rerandomized to tenapanor (=128) or placebo (=127) during the randomized withdrawal period. In the efficacy analysis set (=131), the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was -1.4 mg/dl (<0.0001); in the ITT analysis set (=243), the estimated mean difference was -0.7 mg/dl (=0.002). Loosened stools were the most frequently reported adverse event (53% during the randomized treatment period). Serious adverse events were reported more frequently for participants treated with sevelamer carbonate (16%-23% across the three study periods) compared with tenapanor (11%-17%).
CONCLUSIONS
Tenapanor reduced serum phosphate concentrations and maintained control of serum phosphate in participants receiving maintenance dialysis, with an acceptable safety and tolerability profile.
Topics: Humans; Isoquinolines; Phosphates; Renal Dialysis; Sulfonamides; United States
PubMed: 35372979
DOI: 10.34067/KID.0002002021 -
Current Biology : CB Feb 2021A delayed eating schedule is associated with increased risk of obesity and metabolic dysfunction in humans. However, there are no prolonged, highly controlled... (Randomized Controlled Trial)
Randomized Controlled Trial
A delayed eating schedule is associated with increased risk of obesity and metabolic dysfunction in humans. However, there are no prolonged, highly controlled experimental studies testing the effects of meal timing on weight and metabolism in adults with a body mass index (BMI) of 19-27 kg/m. Twelve healthy adults (age: 26.3 ± 3.4 years; BMI: 21.9 ± 1.7 kg/m; 5 females) participated in a randomized crossover study in free-living conditions. Three meals and two snacks with comparable energy and macronutrient contents were provided during two, 8-week, counterbalanced conditions separated by a 2-week washout period: (1) daytime (intake limited to 0800 h-1900 h) and (2) delayed (intake limited to 1200 h-2300 h). Sleep-wake cycles and exercise levels were held constant. Weight, adiposity, energy expenditure, and circadian profiles of hormones and metabolites were assessed during four inpatient visits occurring before and after each condition. Body weight, insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]), trunk-to-leg fat ratio, resting energy expenditure, respiratory quotient, and fasting glucose, insulin, total and high-density lipoprotein (dHDL) cholesterol, and adiponectin decreased on the daytime compared to the delayed schedule. These measures, as well as triglycerides, increased on the delayed compared to the daytime schedule (effect size range: d = 0.397-1.019). Circadian phase and amplitude of melatonin, cortisol, ghrelin, leptin, and glucose were not differentially altered by the eating schedules. Overall, an 8-week daytime eating schedule, compared to a delayed eating schedule, promotes weight loss and improvements in energy metabolism and insulin in adults with BMI 19-27 kg/m, underscoring the efficacy and feasibility of daytime eating as a behavioral modification for real-world conditions.
Topics: Adult; Circadian Rhythm; Cross-Over Studies; Eating; Energy Metabolism; Female; Glucose; Humans; Insulin; Insulin Resistance; Male; Obesity; Young Adult
PubMed: 33259790
DOI: 10.1016/j.cub.2020.10.092 -
Journal of the American Heart... Sep 2020Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study.
Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4-week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4-week washout period. The primary outcome was difference in oxidized low-density lipoprotein cholesterol (LDL-C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short-chain and branched-chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL-C (-2.73 U/L), total cholesterol (-5.03 mg/dL), LDL-C (-3.87 mg/dL), and body weight (-0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l-carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL-C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL-C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL-C observed with the VD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02942628.
Topics: Aged; Cardiometabolic Risk Factors; Cholesterol, LDL; Cross-Over Studies; Diet, Vegetarian; Fatty Acids; Female; Gastrointestinal Microbiome; Humans; Male; Metabolome; Middle Aged; Myocardial Ischemia
PubMed: 32893710
DOI: 10.1161/JAHA.120.016518 -
BMJ Open May 2020Insomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently...
Cannabidiol (CBD) and Δ-tetrahydrocannabinol (THC) for chronic insomnia disorder ('CANSLEEP' trial): protocol for a randomised, placebo-controlled, double-blinded, proof-of-concept trial.
INTRODUCTION
Insomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder.
METHODS AND ANALYSIS
A randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution ('ETC120') containing 10 mg Δ-tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35-60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated.
ETHICS AND DISSEMINATION
Ethics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences.
TRIAL REGISTRATION NUMBER
ANZCTRN12619000714189.
Topics: Adult; Cannabidiol; Cannabis; Double-Blind Method; Dronabinol; Humans; Middle Aged; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 32430450
DOI: 10.1136/bmjopen-2019-034421 -
British Journal of Haematology Jul 2023For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine...
For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10 /μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3-24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 10 /μL; p = 0.022) or low CD4/CD8 ratios (
washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients. Topics: Humans; Receptors, Chimeric Antigen; T-Lymphocytes; Cohort Studies; Japan; Bendamustine Hydrochloride; Receptors, Antigen, T-Cell; Lymphoma, Large B-Cell, Diffuse; Immunotherapy, Adoptive; Risk Factors
PubMed: 37096915
DOI: 10.1111/bjh.18831 -
Nutrients Mar 2021Ketogenic low-carbohydrate high-fat (LCHF) diets are popular among young, healthy, normal-weight individuals for various reasons. We aimed to investigate the effect of a... (Randomized Controlled Trial)
Randomized Controlled Trial
Ketogenic low-carbohydrate high-fat (LCHF) diets are popular among young, healthy, normal-weight individuals for various reasons. We aimed to investigate the effect of a ketogenic LCHF diet on low-density lipoprotein (LDL) cholesterol (primary outcome), LDL cholesterol subfractions and conventional cardiovascular risk factors in the blood of healthy, young, and normal-weight women. The study was a randomized, controlled, feeding trial with crossover design. Twenty-four women were assigned to a 4 week ketogenic LCHF diet (4% carbohydrates; 77% fat; 19% protein) followed by a 4 week National Food Agency recommended control diet (44% carbohydrates; 33% fat; 19% protein), or the reverse sequence due to the crossover design. Treatment periods were separated by a 15 week washout period. Seventeen women completed the study and treatment effects were evaluated using mixed models. The LCHF diet increased LDL cholesterol in every woman with a treatment effect of 1.82 mM ( < 0.001). In addition, Apolipoprotein B-100 (ApoB), small, dense LDL cholesterol as well as large, buoyant LDL cholesterol increased ( < 0.001, < 0.01, and < 0.001, respectively). The data suggest that feeding healthy, young, normal-weight women a ketogenic LCHF diet induces a deleterious blood lipid profile. The elevated LDL cholesterol should be a cause for concern in young, healthy, normal-weight women following this kind of LCHF diet.
Topics: Adult; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Diet, Carbohydrate-Restricted; Diet, High-Fat; Fatty Acids; Female; Humans; Lipids; Lipoproteins; Risk Factors; Sweden; Young Adult
PubMed: 33801247
DOI: 10.3390/nu13030814