Double-blind Crossover Pilot Study Research Articles

Assessing the Postprandial Impact of Saturated and Polyunsaturated Fatty Acids on Blood Pressure: A Double-Blind Crossover Pilot Study

Assessing the Postprandial Impact of Saturated and Polyunsaturated Fatty Acids on Blood Pressure: A Double-Blind Crossover Pilot Study

TDCS over the temporal cortex to improve the functional capacity of children with cerebral palsy: Randomized, placebo-controlled, double-blind crossover pilot study

tDCS over the temporal cortex to improve the functional capacity of children with cerebral palsy: Randomized, placebo-controlled, double-blind crossover pilot study

Influence of energy drinks on acute hemodynamic parameters in young healthy adults: a randomized double-blind placebo-controlled crossover pilot study

Influence of energy drinks on acute hemodynamic parameters in young healthy adults: a randomized double-blind placebo-controlled crossover pilot study

Music tuned to 432 Hz versus music tuned to 440 Hz for improving sleep in patients with spinal cord injuries: a double-blind cross-over pilot study.

Background and aim of the work.Among people with spinal cord injuries, sleep disorders are considered one of the top well-being priorities. Some studies suggest that listening to music promotes sleep and improves its quality. These studies usually used music standardised at the frequency of 440 Hz. The aim of the present study is to compare the effects of listening to music tuned to 440 Hz and music tuned to 432 Hz on sleep in patients with spinal cord injuries.Methods.Double-blind cross-over pilot study in a single Italian Spinal Unit. 12 patients with spinal injuries were provided with mp3 players loaded with their favourite music tuned to 440 Hz or 432 Hz. They were invited to listen to music for 30 minutes each day, in the two periods of the study. “Sleep Scale for Medical Study” modified for this study, and the “Perceived Stress Scale” were chosen.Results.The participants were eight males (mean age =58.12, SD ±13.62), and four females (mean age =56.25, SD ±14.17). Five were quadriplegics and seven were paraplegics. Listening times and wash-out periods were variable. The stress decreased, but not significantly, with listening to music at both frequencies. After listening to music at 432 Hz there was a significant improvement in sleep scores (+3.6, p=0.02), while there was no improvement in sleep scores listening to music at 440 Hz (-1.50, p=0.34).Conclusions.The results suggest that further studies on music interventions at 432 Hz should be performed. It is advisable to increase sample sizes and use a range of different research methods. (www.actabiomedica.it)

Ubiquinol Improves Endothelial Function in Patients with Heart Failure with Reduced Ejection Fraction: A Single-Center, Randomized Double-Blind Placebo-Controlled Crossover Pilot Study

Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function. We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400mg/day or placebo for 3months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI). Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400mg/day for 3months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39-1.80], post-RHI 1.74 [IQR 1.63-2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53-1.85], post-RHI 1.51 [IQR 1.39-2.11], p = 0.198). Ubiquinol 400mg/day for 3months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed. Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.

Both melatonin and meloxicam improved sleep and pain in females with primary dysmenorrhea-results from a double-blind cross-over intervention pilot study.

Up to 25% of ovulating women suffer from primary dysmenorrhea, a condition associated with pain and transient-reduced quality of life, along with greater irritability and impaired sleep. In the present study, we asked whether and if so to what extent melatonin and meloxicam can improve subjective and objective sleep and reduce pain among women with primary dysmenorrhea (PD). To this end, we conducted a double-blind cross-over clinical trial lasting for three menstrual cycles. A total of 14 women (mean age M = 27.5years) with primary dysmenorrhea took part in the study. At baseline, that is, during the first menstruation, they completed a visual analogue scale to rate pain; sleep continuity was assessed via actigraphs, and overall sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Next, participants were randomly assigned to one of two conditions, either melatonin during the second, and meloxicam during the third menstruation, or meloxicam during the second, and melatonin during the third menstruation. Neither participants nor investigators were aware of participants' study assignment. During the second and third menstruations, the assessments described above were repeated. At baseline, sleep assessed both objectively and subjectively was impaired, and pain was high. Subjective sleep improved and pain decreased during the second and third menstruations irrespective of whether melatonin or meloxicam was administered first or second. Likewise, objective sleep efficiency increased and objective sleep latency shortened. The efficacy of melatonin was superior to that of meloxicam. The present pattern of results suggests that both melatonin and meloxicam are suitable to treat pain and PD-related sleep complaints among women with primary dysmenorrhea.

The optimal stimulation site for high-frequency repetitive transcranial magnetic stimulation in Parkinson’s disease: A double-blind crossover pilot study

Many reports have shown improvements in motor symptoms after repetitive transcranial magnetic stimulation (rTMS). However, the best stimulation area in the brain has not currently been determined. We assessed the effects of high-frequency rTMS (HF-rTMS) on the motor and mood disturbances in Parkinson’s disease (PD) patients and attempted to determine whether the primary motor area (M1), the supplementary motor area (SMA), and the dorsolateral prefrontal cortex (DLPFC) were the best treatment targets. In this randomized, double-blind crossover design study, we investigated the efficacy of 3 consecutive days of HF-rTMS over the M1, SMA, and DLPFC and compared these HF-rTMS to sham stimulations. We used motor and non-motor scales to evaluate the parkinsonian symptoms. The changes in the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) scores after the application of HF-rTMS over the M1 and SMA were significantly greater than those after the sham stimulation. However, after the application of HF-rTMS over the DLPFC, the UPDRS-III scores were similar to those after the sham stimulation. No significant improvements were demonstrated in the mood disturbances after the stimulations over any of the targets. In conclusion, the application of HF-rTMS over the M1 and SMA significantly improved the motor symptoms in the PD patients but did not alter the mood disturbances.

Effect of Oral Pre-Meal Administration of Betaglucans on Glycaemic Control and Variability in Subjects with Type 1 Diabetes.

We conducted a double-blind placebo-controlled crossover pilot study to investigate the effect of oat betaglucans (β-glucan) on glycaemic control and variability in adults with type 1 diabetes (T1D; n = 14). Stomacol® tablets (1.53 g of β-glucan) or placebo (Plac) were administered three times daily before meals for two weeks. Glucose levels were monitored during the second week by continuous glucose monitoring (CGM). There was an increase in basic measures of glycaemic control (maximal glucose value 341 ± 15 vs. 378 ± 13 mg/dL for Plac and β-glucan, p = 0.004), and average daily risk range (62 ± 5 vs. 79 ± 4 mg/dL for Plac and β-glucan, p = 0.003) favouring Plac over β-glucan, but no increase in the M-value (the weighted average of the glucose values) or other more complex measures. Basic measures of glucose variability were also slightly increased during β-glucan treatment, with no difference in more complex measures. However, glycaemic variability increased between the first and last two CGM days on Plac, but remained unchanged on β-glucan. In conclusion, in this pilot study we were unable to demonstrate a general positive effect of β-glucan before meals on glucose control or variability in T1D.

Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent chest pain or dyspnea despite optimal medical and revascularization therapy: randomized, double-blind crossover pilot study.

BackgroundPatients with ischemic cardiomyopathy (ICM) may continue to experience persistent chest pain and/or dyspnea despite pharmacologic therapy and revascularization. We hypothesized that ranolazine would reduce anginal symptoms or dyspnea in optimally treated ICM patients.MethodsIn this randomized, double-blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less or equal 40%) were included after providing informed consent. A total of 24 patients completed both placebo and ranolazine treatments and were analyzed. All patients were on treatment with a beta blocker, an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker), and at least one additional antianginal drug. After randomization, patients received up to 1,000 mg ranolazine orally twice a day, as tolerated, versus placebo. The primary end point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ), or in dyspnea as assessed by the Rose Dyspnea Scale (RDS). Change in the RDS and SAQ score from baseline was compared, for ranolazine and placebo, using the Wilcoxon signed rank test or paired t-test.ResultsPatients had the following demographic and clinical variables: mean age of 71.5 years; male (82.1%); prior coronary bypass surgery (67.9%); prior coronary percutaneous intervention (85.7%); prior myocardial infarction (82.1%); diabetes (67.9%); and mean ejection fraction of 33.1%. No statistical difference was seen between baseline RDS score and that after placebo or ranolazine (n=20) (P≥0.05). There was however, an improvement in anginal frequency (8/10 patients) (P=0.058), quality of life (8/10 patients) (P=0.048), and mean score of all components of the SAQ questionnaire (n=10) (P=0.047) with ranolazine compared with placebo.ConclusionIn optimally treated ICM patients with continued chest pain or dyspnea, ranolazine possibly had a positive impact on quality of life, a reduction in anginal frequency, and an overall improvement in the mean SAQ component score compared with baseline. Ranolazine did not change the dyspnea score compared with baseline.

High-protein, low-fat, short-term diet results in less stress and fatigue than moderate-protein moderate-fat diet during weight loss in male weightlifters: a pilot study.

Athletes risk performance and muscle loss when dieting. Strategies to prevent losses are unclear. This study examined the effects of two diets on anthropometrics, strength, and stress in athletes. This double-blind crossover pilot study began with 14 resistance-trained males (20-43 yr) and incurred one dropout. Participants followed carbohydrate-matched, high-protein low-fat (HPLF) or moderate-protein moderate-fat (MPMF) diets of 60% habitual calories for 2 weeks. Protein intakes were 2.8g/kg and 1.6g/kg and mean fat intakes were 15.4% and 36.5% of calories, respectively. Isometric midthigh pull (IMTP) and anthropometrics were measured at baseline and completion. The Daily Analysis of Life Demands of Athletes (DALDA) and Profile of Mood States (POMS) were completed daily. Outcomes were presented statistically as probability of clinical benefit, triviality, or harm with effect sizes (ES) and qualitative assessments. Differences of effect between diets on IMTP and anthropometrics were likely or almost certainly trivial, respectively. Worse than normal scores on DALDA part A, part B and the part A "diet" item were likely more harmful (ES 0.32, 0.4 and 0.65, respectively) during MPMF than HPLF. The POMS fatigue score was likely more harmful (ES 0.37) and the POMS total mood disturbance score (TMDS) was possibly more harmful (ES 0.29) during MPMF than HPLF. For the 2 weeks observed, strength and anthropometric differences were minimal while stress, fatigue, and diet-dissatisfaction were higher during MPMF. A HPLF diet during short-term weight loss may be more effective at mitigating mood disturbance, fatigue, diet dissatisfaction, and stress than a MPMF diet.

Somatropin treatment of spinal muscular atrophy: A placebo-controlled, double-blind crossover pilot study

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n=19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03mg/kg/day) or placebo subcutaneously for 3months, followed by a 2-month wash-out phase before 3months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08N, 95% confidence interval (CI:−3.79;3.95, p=0.965), lower limb muscle strength (point estimate mean: 2.23N, CI:−2.19;6.63, p=0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III.

American ginseng does not improve fatigue in multiple sclerosis: a single center randomized double-blind placebo-controlled crossover pilot study

This study examined the safety and efficacy of an escalating dose (100 mg, 200 mg, 400 mg/day) of American ginseng over 6 weeks in a single-center, randomized, double-blind, placebo-controlled, crossover trial with 56 subjects with multiple sclerosis and fatigue. There were no serious adverse events but fatigue on ginseng, as assessed by the Fatigue Severity Scale, was not significantly different from fatigue on placebo.

Rate responsive pacing using cardiac resynchronization therapy in patients with chronotropic incompetence and chronic heart failure

Chronotropic incompetence (CI) is a common finding in patients with advanced chronic heart failure (CHF) and is associated with a worse functional capacity. Whether rate responsive pacing with cardiac resynchronization therapy (CRT) would acutely improve exercise performance in patients with advanced CHF and severe CI (<70% age-predicted maximum heart rate) is unknown. Patients (n = 13) with CHF, a CRT device, and severe CI were randomized in a double-blind crossover pilot study to either DDD (control) or DDDR (rate responsive) pacing. Six minutes walk test (6MWT) distance, oxygen consumption at anaerobic threshold (VO(2) @ AT), and maximal oxygen consumption (VO(2) max) were measured. One week later, testing was repeated in the alternate pacing mode. Rate responsive pacing commenced with standard settings in only 9 of 13 (69%) patients. In these 9 subjects, 6MWT distance improved acutely from 358.5 ± 40.7 to 376.8 ± 24.5 m with DDDR pacing (P< 0.05). VO(2) max did not improve with DDDR pacing (14.0 ± 3.2 mL/kg/min) compared with DDD pacing (13.9 ± 3.0 mL/kg/min; P= 0.69). VO(2) @ AT tended towards improvement with DDDR pacing (10.8 ± 2.9 mL/kg/min) compared with DDD pacing (9.6 ± 1.8 mL/kg/min; P= 0.29). There was a linear relationship between the increase in heart rate at minute 3 during rate responsive pacing and improvement in VO(2) @ AT (r = 0.83, P< 0.05). When rate responsive pacing using a CRT device is achieved in patients with advanced CHF and severe CI, parameters of aerobic exercise performance improve acutely. Routine exercise testing to ensure successful restoration of heart rate response may be beneficial to optimize CRT settings in this patient population.

Vasopressin therapy in Parkinson's disease.

A double-blind crossover pilot study was carried out in six patients with Parkinson's disease in order to test the possible therapeutic effect of L-vasopressin after treatment for 1 month with 30 I.U. intranasally daily. The investigation was completed in five cases. No effects was noticed after LVP treatment.

Terbutaline and the Prevention of Nocturnal Hypoglycemia in Type 1 Diabetes

OBJECTIVE—Bedtime administration of 5.0 mg of the β2-adrenergic agonist terbutaline prevents nocturnal hypoglycemia but causes morning hyperglycemia in type 1 diabetes. We tested the hypothesis that 2.5 mg terbutaline prevents nocturnal hypoglycemia without causing morning hyperglycemia.RESEARCH DESIGN AND METHODS—This was a randomized double-blind crossover pilot study (placebo, 2.5 mg terbutaline, and 5.0 mg terbutaline) in 15 patients with type 1 diabetes.RESULTS—Mean ± SE nadir nocturnal plasma glucose concentrations were 87 ± 14 mg/dl following placebo, 100 ± 14 mg/dl following 2.5 mg terbutaline, and 122 ± 13 mg/dl following 5.0 mg terbutaline (P < 0.05 vs. placebo). Nadir levels were <50 mg/dl in 5, 2, and 0 patients (P < 0.05 vs. placebo), respectively. Morning levels were 113 ± 18, 127 ± 17, and 183 ± 19 mg/dl (P < 0.02 vs. placebo), respectively.CONCLUSIONS—Terbutaline may be shown to be effective and safe in the prevention of nocturnal hypoglycemia in type 1 diabetes in a suitably powered randomized controlled trial.

Caffeine as an Adjuvant to Ibuprofen in Treating Childhood Headaches

In adults, caffeine has been shown to enhance the effectiveness of most analgesics, including ibuprofen. This double-blind cross-over pilot study evaluated the effect of ibuprofen and caffeine compared with ibuprofen and placebo in 12 children with headaches. Patients completed diaries for both headaches. Outcome measures included a five-faces severity scale, a measure of clinical disability, and a scale of pain severity. Comparison of the cumulative response scores revealed a trend toward a greater response to ibuprofen-caffeine treatment of headaches (P = 0.14, P = 0.09, and P = 0.07 for the three measures, respectively). Further larger studies are needed to confirm this effect and to identify potential responders.

A novel starch for the treatment of glycogen storage diseases

To determine whether a new starch offers better short-term metabolic control than uncooked cornstarch in patients with glycogen storage diseases (GSDs). A short-term double-blind cross-over pilot study comparing uncooked physically modified cornstarch (WMHM20) with uncooked cornstarch in patients with GSD types Ia, Ib and III. Twenty-one patients (ages 3-47, 9 female) were given 2 g/kg cornstarch or WMHM20 mixed in water. Blood glucose, lactate and insulin, and breath hydrogen and (13)CO2 enrichment were measured, at baseline and after each load. The hourly biochemical evaluations terminated when blood glucose was < or = 3.0 mmol/L, when the study period had lasted 10 h or when the patient wished to end the test. The alternative starch was administered under similar trial conditions a median of 10 days later. The median starch load duration was 9 h for WMHM20 versus 7 h for cornstarch. Glucose decreased more slowly (p = 0.05) and lactate was suppressed faster (p = 0.17) for WMHM20 compared with cornstarch. Peak hydrogen excretion was increased (p = 0.05) when cornstarch was taken. These data indicate longer duration of euglycaemia and better short-term metabolic control in the majority of GSD patients with WMHM20 compared to cornstarch.

Urinary excretion of equol by postmenopausal women consuming soymilk fermented by probiotic bifidobacteria

To study the effects of consuming isoflavone aglycone-enriched soymilk fermented by bifidobacteria on urinary excretion of equol with respect to fermentation, daidzein dose, supplementation duration and background diet. Double-blind crossover pilot study comprising three 14-day supplementation periods separated by a washout. Victoria University, Melbourne, Australia. Sixteen postmenopausal women. SUBJECTS randomized into two groups consuming either fermented (FS) or non-fermented soymilk (NFS), ingested three daily dosages of daidzein via soymilk and collected pooled urine specimens. Daidzein and equol were quantified using high-performance liquid chromatography. After 14-days supplementation six women (38%) excreted equol (>1 micromol equol/day), including four from the FS group, two of whom were classified as non-producers at day 4. Bifidobacteria ingestion, composition of daidzein and its glucosides, and carbohydrate intake appeared to influence equol formation among equol producers. Pilot-study group mean urinary equol excretion results provided insufficient evidence (P>0.05) that FS consumption instigates equol production in women predetermined as non-producers.

Effects of Lithium on Saccadic Eye Movements in Healthy Subjects in a Ten-Day Double-Blind Placebo-Controlled Cross-Over Pilot Study

Although previous studies have shown that lithium modifies eye movements or psychomotor speed, no studies have ever explored the predictive saccades or memory guided saccades during lithium administration. We took the objective to determine the influence of lithium in pseudo-random, predictive or memory-guided saccades in healthy subjects with a view to detect reduced psychomotor speed, inability to anticipate incoming events, or working memory deficits. A ten day lithium-placebo randomized double-blind cross-over pilot study was carried out with 12 healthy male volunteers. The cognitive assessment included pseudo-random, predictive and memory guided saccades before and after lithium and placebo periods. A biological assay substantiated the lithium effect on TSH and thyroid hormones. There was no change in pseudo-random or memory guided saccades when comparing lithium or placebo administration. However the ratio of anticipated saccades decreased under the lithium sequence while it remained stable under placebo. Also, subjects having lithium serum levels of > 0.5 meq/l had longer latencies in anticipated saccades. The findings do not support a major effect of lithium on alertness or on working memory, although the dosage and duration of lithium was sufficient to modify TSH blood level. Nevertheless, lithium treatment was associated with decreased anticipation in predictive saccades, suggesting this could reflect a reduced ability to anticipate quick motor movements and could be related to the well-known effect of lithium as an anti-impulsive medication.

THE EFFECT OF ISOLATED SOY PROTEIN ON PLASMA BIOMARKERS IN ELDERLY MEN WITH ELEVATED SERUM PROSTATE SPECIFIC ANTIGEN

We performed a randomized double-blind crossover pilot study in elderly men with elevated prostate specific antigen (PSA) on the effects of the daily consumption of 2 soy beverages, each containing 20 gm. of isolated soy protein, on the isoflavone concentration in blood and urine, and on the 3 serum biomarkers cholesterol, PSA and the soluble p105 component of the p185erbB-2 proto-oncogene. A total of 34 men supplemented their diet by consuming 1 of 2 soy protein beverages assigned randomly twice daily for a 6-week period. In a second 6-week period they consumed the other soy protein beverage. The beverage ISP+ provided 42 mg. of genistein and 27 mg. of daidzein daily, whereas the other beverage, ISP-, provided only 2.1 and 1.3 mg. of these isoflavones daily, respectively. Blood and 24-hour urine samples were obtained before the study, at 2-week intervals during the study and 2 weeks after study completion. ISP+ and to a lesser extent ISP- substantially increased the serum concentration and urinary output of the isoflavones and their metabolites. Serum cholesterol was significantly decreased by ISP+ irrespective of the order in which the 2 soy beverages were administered and in apparent correlation with the total isoflavone concentration. There was no significant effect of the soy beverages on serum PSA and p105erbB-2 values. This study reveals that short-term exposure of elderly men with elevated serum PSA values to soy protein containing isoflavones decreases serum cholesterol but not the serum biomarkers PSA and p105erbB-2.