-
1.
A Randomized Double-Blind, Cross-Over Trial of very Low-Calorie Diet in Overweight Migraine Patients: A Possible Role for Ketones?
Di Lorenzo, C, Pinto, A, Ienca, R, Coppola, G, Sirianni, G, Di Lorenzo, G, Parisi, V, Serrao, M, Spagnoli, A, Vestri, A, et al
Nutrients. 2019;11(8)
-
-
-
Free full text
Plain language summary
The ketogenic diet (KD) constitutes high-fat, adequate protein, and low-carbohydrate, and has been proven to be efficacious for the treatment of drug-resistant epilepsy. Recently, KD showed promising results for treating other neurological conditions. The aim of this study was to analyse the effects of very low-calorie ketogenic diets (VLCKDs) in overweight episodic migraine patients during a weight-loss intervention. This study is a double-blind cross-over design randomised trial (of five phases). Participants eligible for trial participation were overweight/obese adults, aged 18 to 65 years, who had at least 12 months’ history of migraines with or without aura. Subjects alternated randomly between a very low-calorie ketogenic diet and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. Results indicate that a 4-week period VLCKD, despite inducing similar weight loss and glycaemic profile, was significantly more effective than VLCnKD in preventing migraine attacks, as evidenced by a decrease in the frequency of migraine days and attacks, and a greater than 50% response rate. Authors conclude that VLCKD is effective for rapid, short-term improvement of migraines in overweight patients, while VLCnKD is not.
Abstract
Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a very low-calorie ketogenic diet (VLCKD) and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. In a nutritional program, 35 overweight obese migraine sufferers were allocated blindly to 1-month successive VLCKD or VLCnKD in random order (VLCKD-VLCnKD or VLCnKD-VLCD). The primary outcome measure was the reduction of migraine days each month compared to a 1-month pre-diet baseline. Secondary outcome measures were 50% responder rate for migraine days, reduction of monthly migraine attacks, abortive drug intake and body mass index (BMI) change. Only data from the intention-to-treat cohort (n = 35) will be presented. Patients who dropped out (n = 6) were considered as treatment failures. Regarding the primary outcome, during the VLCKD patients experienced -3.73 (95% CI: -5.31, -2.15) migraine days respect to VLCnKD (p < 0.0001). The 50% responder rate for migraine days was 74.28% (26/35 patients) during the VLCKD period, but only 8.57% (3/35 patients) during VLCnKD. Migraine attacks decreased by -3.02 (95% CI: -4.15, -1.88) during VLCKD respect to VLCnKD (p < 0.00001). There were no differences in the change of acute anti-migraine drug consumption (p = 0.112) and BMI (p = 0.354) between the 2 diets. A VLCKD has a preventive effect in overweight episodic migraine patients that appears within 1 month, suggesting that ketogenesis may be a useful therapeutic strategy for migraines.
-
2.
A phase II randomized controlled trial of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.
Alibhai, SMH, Santa Mina, D, Ritvo, P, Tomlinson, G, Sabiston, C, Krahn, M, Durbano, S, Matthew, A, Warde, P, O'Neill, M, et al
BMC cancer. 2019;19(1):2
-
-
-
Free full text
Plain language summary
Most men diagnosed with prostate cancer receive androgen deprivation therapy (ADT) and they commonly experience adverse side effects. Exercise is one of the most effective interventions to counter ADT side effects. The main aim of this study was to determine the feasibility of conducting a large multi-centre non-inferiority RCT of three exercise delivery models in men with prostate cancer on ADT. The study is a randomized phase II non-inferiority trial recruited 59 patients who were diagnosed with prostate cancer at any stage. The study compared 1:1, site-based personal training with two less-resource-intense approaches: group, site-training and individual home-based training. Results indicate that exercise adherence, as measured through attendance, was high for supervised sessions but under 50% by self-report and accelerometery. There was no difference between the three groups in terms of satisfaction. Authors conclude that both group, site-training and individual home-based training interventions in men with prostate cancer on ADT appeared to be similar to 1:1, site-based personal training for multiple efficacy outcomes.
Abstract
BACKGROUND Existing evidence demonstrates that 1:1 personal training (PT) improves many adverse effects of androgen deprivation therapy (ADT). Whether less resource-intensive exercise delivery models are as effective remains to be established. We determined the feasibility of conducting a multi-center non-inferiority randomized controlled trial comparing PT with supervised group (GROUP) and home-based (HOME) exercise programs, and obtained preliminary efficacy estimates for GROUP and HOME compared to PT on quality of life (QOL) and physical fitness. METHODS Men with prostate cancer on ADT were recruited from one of two experienced Canadian centres and randomized 1:1:1 to PT, GROUP, or HOME. Randomization was stratified by length of ADT use and site. Participants completed moderate intensity aerobic and resistance exercises 4-5 days per week for 6 months with a target 150 min per week of exercise. Exercise prescriptions were individualized and progressed throughout the trial. Feasibility endpoints included recruitment, retention, adherence, and participant satisfaction. The efficacy endpoints QOL, fatigue, and fitness (VO2 peak, grip strength, and timed chair stands) in GROUP and HOME were compared for non-inferiority to PT. Descriptive analyses were used for feasibility endpoints. Between-group differences for efficacy endpoints were examined using Bayesian linear mixed effects models. RESULTS Fifty-nine participants (mean age 69.9 years) were enrolled. The recruitment rate was 25.4% and recruitment was slower than projected. Retention was 71.2%. Exercise adherence as measured through attendance was high for supervised sessions but under 50% by self-report and accelerometry. Satisfaction was high and there was no difference in this measure between all three groups. Between-group differences (comparing both GROUP and HOME to PT) were smaller than the minimum clinically important difference on most measures of QOL, fatigue, and fitness. However, two of six outcomes for GROUP and four of six outcomes for HOME had a > 20% probability of being inferior for GROUP. CONCLUSIONS Feasibility endpoints were generally met. Both GROUP and HOME interventions in men with PC on ADT appeared to be similar to PT for multiple efficacy outcomes, although conclusions are limited by a small sample size and cost considerations have not been incorporated. Efforts need to be targeted to improving recruitment and adherence. A larger trial is warranted. TRIAL REGISTRATION ClinicalTrials.gov: NCT02046837 . Date of registration: January 20, 2014.
-
3.
Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus.
Cervenka, MC, Hocker, S, Koenig, M, Bar, B, Henry-Barron, B, Kossoff, EH, Hartman, AL, Probasco, JC, Benavides, DR, Venkatesan, A, et al
Neurology. 2017;88(10):938-943
-
-
-
Free full text
-
Plain language summary
Superrefractory status epilepticus (SRSE) is a neurologic emergency that persists despite anti-seizure medication. The ketogenic diet (KD) has been shown to be successful for treating epilepsy and recent retrospective studies suggest KD may be effective for treating SRSE. The aim of this clinical trial was to investigate the feasibility, safety and efficacy of a ketogenic diet on SRSE in adults. After screening, this prospective multi-centre study enrolled 15 participants with SRSE. Participants received a classic ketogenic diet via gastronomy tube. Of the 14 participants whom completed KD treatment SRSE resolved in 11 participants. Five patients ultimately died. This study found KD is feasible in adults with SRSE, and further randomised controlled trials are required to establish comparative safety and efficacy.
Abstract
OBJECTIVE To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults. METHODS We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility. Secondary measures included resolution of SRSE, disposition at discharge, KD-related side effects, and long-term outcomes. RESULTS Twenty-four adults were screened for participation at 5 medical centers, and 15 were enrolled and treated with a classic KD via gastrostomy tube for SRSE. Median age was 47 years (interquartile range [IQR] 30 years), and 5 (33%) were male. Median number of antiseizure drugs used before KD was 8 (IQR 7), and median duration of SRSE before KD initiation was 10 days (IQR 7 days). KD treatment delays resulted from intravenous propofol use, ileus, and initial care received at a nonparticipating center. All patients achieved ketosis in a median of 2 days (IQR 1 day) on KD. Fourteen patients completed KD treatment, and SRSE resolved in 11 (79%; 73% of all patients enrolled). Side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, hyponatremia, and weight loss. Five patients (33%) ultimately died. CONCLUSIONS KD is feasible in adults with SRSE and may be safe and effective. Comparative safety and efficacy must be established with randomized placebo-controlled trials. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that in adults with SRSE, a KD is effective in inducing ketosis.
-
4.
Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study.
Wesa, KM, Cunningham-Rundles, S, Klimek, VM, Vertosick, E, Coleton, MI, Yeung, KS, Lin, H, Nimer, S, Cassileth, BR
Cancer immunology, immunotherapy : CII. 2015;64(2):237-47
-
-
-
Free full text
-
Plain language summary
Myelodysplastic syndromes (MDS) are a group of bone marrow stem cell disorders characterized by ineffective red blood cell production, a reduction in mature blood cells and may progress to acute myelogenous leukaemia (AML). Low levels and poor function of white blood cells, a key part of the immune system, are a common feature of MDS and this increases the risk of serious infection, the most common cause of death in lower-risk MDS patients. Maitake had previously been shown to enhance blood forming cells and was therefore thought to be of potential benefit for MDS patients. The aim of this phase II, open-label, non-randomized, safety and efficacy trial was to assess white blood cells function in lower-risk MDS patients. 18 untreated patients received Maitake extract at 6 mg/kg daily for 12 weeks. The function of two types of white blood cells, neutrophils and monocytes,increased after 12 weeks of maitake administration. Maitake was generally well tolerated although a mild increase in eosinophils, a type of white blood cells associated with allergies, was noted in four patients, and two of these patients also experienced mild diarrhoea. The authors concluded that maitake beta-glucan consumption improves white blood cell (neutrophil and monocyte) function in lower-risk MDS patients and may enhance immune responses against bacterial infection. They point out that one limitation of their trial was a lack of control group and that larger studies are needed to confirm the potential benefits of maitake.
Abstract
BACKGROUND Myelodysplastic syndromes (MDS) are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia. Maitake mushroom beta-glucan, a dietary supplement, stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury. This phase II trial examined the effects of Maitake on innate immune function in MDS. METHODS Myelodysplastic syndromes patients with International Prognostic Scoring System Low- and Intermediate-1-risk disease received oral Maitake extract at 3 mg/kg twice daily for 12 weeks. Primary endpoints included neutrophil count and function tested as endogenous or stimulated neutrophil production of reactive oxygen species (ROS) by flow cytometry compared with age-matched healthy controls (HC). ROS activators were Escherichia coli, phorbol ester, and the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Complete blood counts, chemistry panels, iron studies, and monocyte function were evaluated. RESULTS Of 21 patients enrolled, 18 completed the study and were evaluable. Maitake increased endogenous (basal) neutrophil (p = 0.005) and monocyte function (p = 0.021). Pre-treatment monocyte response to E. coli was reduced in MDS patients compared with HC (p = 0.002) and increased (p = 0.0004) after treatment. fMLP-stimulated ROS production response also increased (p = 0.03). Asymptomatic eosinophilia occurred in 4 patients (p = 0.014). Other changes in albumin, hemoglobin, and total protein were not clinically relevant. CONCLUSIONS Maitake was well tolerated. Enhanced in vitro neutrophil and monocyte function following treatment demonstrate that Maitake has beneficial immunomodulatory potential in MDS. Further study is warranted.
-
5.
The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial.
Mortensen, SA, Rosenfeldt, F, Kumar, A, Dolliner, P, Filipiak, KJ, Pella, D, Alehagen, U, Steurer, G, Littarru, GP
JACC. Heart failure. 2014;2(6):641-9
-
-
-
Free full text
Plain language summary
Optimal therapy of heart failure (HF) is a considerable challenge. Standard treatments are administered to block rather than to enhance cellular processes. Coenzyme Q10 (CoQ10) is a powerful lipid-soluble antioxidant. This study is a prospective, randomized, double-blind, placebo-controlled, multi-centre trial of CoQ10 as adjunctive treatment of chronic HF focusing on changes in symptoms, biomarker status, and long-term outcome. A total of 420 patients were randomly assigned to active treatment with CoQ10 (n = 202) or placebo (n = 218). Results show that supplementation with CoQ10 significantly reduced major adverse cardiovascular events and cardiovascular death by 43% and all-cause mortality by 42%. Furthermore, CoQ10 supplementation improved the patients’ symptoms according to the New York Heart Association functional classification after 2 years. Authors conclude that treatment with CoQ10 in addition to standard therapy for patients with moderate to severe HF is safe, well tolerated, and associated with a reduction in symptoms and major adverse cardiovascular events.
Abstract
OBJECTIVES This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF). BACKGROUND CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints. METHODS Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis. RESULTS A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028). CONCLUSIONS Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).
-
6.
A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects.
Deng, G, Lin, H, Seidman, A, Fornier, M, D'Andrea, G, Wesa, K, Yeung, S, Cunningham-Rundles, S, Vickers, AJ, Cassileth, B
Journal of cancer research and clinical oncology. 2009;135(9):1215-21
-
-
-
Free full text
-
Plain language summary
Grifola frondosa (maitake) is a medicinal mushroom which has been shown to be able to modulate the immune system. Many cancer patients use maitake extracts, however, evidence from clinical trials is lacking. This open label trial set out to determine the optimal dose of maitake extract based on possible toxic effects and blood parameters reflecting the state of the immune system. Eligible patients (post-menopausal women with previously treated breast cancer who were free of disease) were sequentially allocated to one of five groups (six subjects in each group) who received 0.2, 1, 3, 6 and 10 mg/kg of liquid maitake extract, respectively, daily for three weeks. Bloods were taken prior to the study beginning and on days 7, 14 and 21. No adverse effects or toxicities were observed. There were statistically significant dose response relationships for 25 out of the 146 parameters measured, with a stimulatory effect on some parameters, and a suppressing on others. The authors concluded that maitake was well tolerated and was associated with significant effects on immune balance, however, the effects were complex and depended on the different cell types and cytokines (specific signalling molecules of the immune system) evaluated, suggesting that maitake should be seen as an immune “modulator” rather than “enhancer”. The study was not designed to evaluate clinical efficacy of maitake.
Abstract
BACKGROUND Cancer patients commonly use dietary supplements to "boost immune function". A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown. METHODS In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days -7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability. RESULTS No dose-limiting toxicity was encountered. Two patients withdrew prior to completion of the study due to grade I possibly related side effects: nausea and joint swelling in one patient; rash and pruritus in the second. There was a statistically significant association between Maitake and immunologic function (p < 0.0005). Increasing doses of Maitake increased some immunologic parameters and depressed others; the dose-response curves for many endpoints were non-monotonic with intermediate doses having either immune enhancing or immune suppressant effects compared with both high and low doses. CONCLUSIONS Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. Cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function.