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Nutrients May 2024The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D formulations (softgels) in healthy adults, at single daily doses of... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D 1000 IU (STD1000), (2) micellar Vitamin D 1000 IU (LMD1000), (3) standard Vitamin D 2500 IU (STD2500), and (4) micellar Vitamin D 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5-60): 992 ± 260 vs. 177 ± 140 nmol day/L; < 0.05, suggesting up to 6 times higher Vitamin D absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D concentrations than the STD1000 group (iAUC(30-60): 680 ± 190 vs. 104 ± 91 nmol day/L; < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D (LipoMicel), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.
Topics: Humans; Pilot Projects; Cholecalciferol; Male; Female; Double-Blind Method; Adult; Dietary Supplements; Micelles; Biological Availability; Administration, Oral; Middle Aged; Young Adult; Calcifediol; Vitamin D
PubMed: 38892507
DOI: 10.3390/nu16111573 -
Nutrients May 2024Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this... (Randomized Controlled Trial)
Randomized Controlled Trial
Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this alteration plays a role in NAFLD pathogenesis. We investigated whether prebiotic administration affects liver fat content and/or liver-related and metabolic parameters. Patients with NAFLD and metabolic syndrome (age: 50 ± 11; 79% men) were randomized to receive either 16 g/day of prebiotic (ITFs-inulin-type fructans) ( = 8) or placebo (maltodextrin) ( = 11) for 12 weeks. Patients were instructed to maintain a stable weight throughout the study. Liver fat content (measured by HMRS), fecal microbiota, and metabolic, inflammatory, and liver parameters were determined before and after intervention. Fecal samples from patients who received the prebiotic had an increased content of ( = 0.025), which was not observed with the placebo. However, the baseline and end-of-study liver fat contents did not change significantly in the prebiotic and placebo groups, neither did the liver function tests' metabolic and inflammatory mediators, including fibroblast growth factor-19 and lipopolysaccharide-binding protein. Body weight remained stable in both groups. These findings suggest that prebiotic treatment without weight reduction is insufficient to improve NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Prebiotics; Male; Middle Aged; Female; Pilot Projects; Gastrointestinal Microbiome; Adult; Liver; Feces; Bifidobacterium; Double-Blind Method; Metabolic Syndrome
PubMed: 38892505
DOI: 10.3390/nu16111571 -
Nutrients May 2024Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized...
Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo ( < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.
Topics: Humans; Middle Aged; Homocysteine; Female; Male; Dietary Supplements; Methylenetetrahydrofolate Reductase (NADPH2); Double-Blind Method; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Cholesterol, LDL; Aged; Vitamin B 12; Pyridoxal Phosphate; Adult; Ferredoxin-NADP Reductase; Tetrahydrofolates; Polymorphism, Genetic; Vitamin B Complex
PubMed: 38892484
DOI: 10.3390/nu16111550 -
International Journal of Molecular... May 2024Emerging research links the endocannabinoid system to gut microbiota, influencing nociception, mood, and immunity, yet the molecular interactions remain unclear. This... (Randomized Controlled Trial)
Randomized Controlled Trial
Emerging research links the endocannabinoid system to gut microbiota, influencing nociception, mood, and immunity, yet the molecular interactions remain unclear. This study focused on the effects of probiotics on ECS markers-cannabinoid receptor type 2 (CB2) and fatty acid amide hydrolase (FAAH)-in dancers, a group selected due to their high exposure to physical and psychological stress. In a double-blind, placebo-controlled trial (ClinicalTrials.gov NCT05567653), 15 dancers were assigned to receive either a 12-week regimen of Rosell-52 and Rosell-17 or a placebo (PLA: = 10, PRO: = 5). There were no significant changes in CB2 (probiotic: 0.55 to 0.29 ng/mL; placebo: 0.86 to 0.72 ng/mL) or FAAH levels (probiotic: 5.93 to 6.02 ng/mL; placebo: 6.46 to 6.94 ng/mL; > 0.05). A trend toward improved sleep quality was observed in the probiotic group, while the placebo group showed a decline (PRO: from 1.4 to 1.0; PLA: from 0.8 to 1.2; = 0.07841). No other differences were noted in assessed outcomes (pain and fatigue). Probiotic supplementation showed no significant impact on CB2 or FAAH levels, pain, or fatigue but suggested potential benefits for sleep quality, suggesting an area for further research.
Topics: Humans; Probiotics; Endocannabinoids; Female; Double-Blind Method; Fatigue; Adult; Male; Pain; Sleep; Amidohydrolases; Young Adult; Receptor, Cannabinoid, CB2; Gastrointestinal Microbiome; Adolescent
PubMed: 38891799
DOI: 10.3390/ijms25115611 -
Journal of Hematology & Oncology Jun 2024Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in...
Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.
BACKGROUND
Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance.
METHODS
Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC.
RESULTS
We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC.
CONCLUSIONS
The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.
Topics: Humans; Esophageal Neoplasms; Male; Female; Prospective Studies; Middle Aged; DNA Methylation; Double-Blind Method; Aged; Biomarkers, Tumor; Cell-Free Nucleic Acids; Adult
PubMed: 38890756
DOI: 10.1186/s13045-024-01565-2 -
BMC Complementary Medicine and Therapies Jun 2024Insomnia is common in college students, but its impact on health and wellbeing is often neglected. Enhancing sleep quality through targeted interventions could improve... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Insomnia is common in college students, but its impact on health and wellbeing is often neglected. Enhancing sleep quality through targeted interventions could improve overall health and reduce the risk of consequent co-morbidities and mental health problems. Qigong exercises have been shown to significantly improve sleep quality and relieve insomnia. Three-circle Post Standing (TCPS) can help integrate body, breath, and mind, a fundamental principle of Qigong that promotes holistic wellbeing. In this clinical trial, we aim to (1) evaluate the feasibility, safety, and therapeutic efficacy of administering TCPS to improve sleep quality and quality of life in college students with insomnia; (2) explore the neurophysiological mechanisms underlying the mind adjustments mediated by TCPS in insomnia; (3) investigate body and breath pathophysiology mediated by TCPS in insomnia; and (4) assess the long-term efficacy of TCPS in terms of sleep quality and quality of life.
METHODS
This will be a prospective, parallel, four-arm, double-blind randomized controlled trial to investigate the effects and underlying mechanisms of TCPS on college students with insomnia. One hundred college students meeting diagnostic criteria for insomnia will be randomly assigned to receive either 14 weeks of standardized TCPS training (two weeks of centralized training followed by 12 weeks of supervised training) or sham-control Post Standing training. Efficacy outcomes including sleep quality, quality of life, neurophysiological assessments, plantar pressure, biomechanical balance, and physical measures will be collected at baseline, eight weeks (mid-point of supervised training), and 14 weeks (end of supervised training). Sleep quality and quality of life will also be evaluated during the four- and eight-week follow-up.
DISCUSSION
This trial will be an important milestone in the development of new therapeutic approaches for insomnia and should be easily implementable by college students with insomnia. The neuro- and pathophysiological assessments will provide new insights into the mechanisms underlying TCPS.
CLINICAL TRIAL REGISTRATION
This trial has been registered in the China Clinical Trials Registry (registration number: ChiCTR2400080763).
Topics: Humans; Sleep Initiation and Maintenance Disorders; Qigong; Students; Double-Blind Method; Universities; Young Adult; Quality of Life; Prospective Studies; Male; Adult; Female; Sleep Quality
PubMed: 38890651
DOI: 10.1186/s12906-024-04544-9 -
BMC Women's Health Jun 2024The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP).
METHODS
SCHUMANN was a randomized, placebo- and active comparator-controlled, double-blind to placebo and open-label to comparator, parallel-group, multicenter, dose-finding phase 2b study. The participants were women with surgically diagnosed endometriosis who fulfilled defined EAPP criteria. Participants were randomized 1:1:1:1 to twice daily (BID) 25 mg, 75 mg, or 150 mg oral eliapixant or a placebo for 12 weeks. An exploratory once-daily elagolix 150 mg treatment group was also included. The primary endpoint was the absolute change in mean worst EAPP from baseline to the end of intervention (EOI).
RESULTS
Overall, 215 participants were randomized for treatment (44 to eliapixant 25 mg, 44 to eliapixant 75 mg, 43 to eliapixant 150 mg, 43 to a placebo, and 41 to elagolix 150 mg). For safety reasons, the study was terminated early; both treatment and enrollment stopped immediately, producing less than 50% of the planned number of completers. The study found no significant differences in EAPP reduction from baseline between groups and no significant dose-response model. The elagolix 150 mg group showed better pain reduction than any of the other groups. No new safety signals were observed, relative to the previously known safety profile of eliapixant, which was generally well tolerated. However, one case of moderate and probably drug-induced liver injury in a participant receiving eliapixant 150 mg BID supported the association between eliapixant and a potential increase in liver function values, defined before the start of the phase 2 program.
CONCLUSIONS
This study did not meet its primary objective as no statistically significant or clinically relevant differences in changes of mean worst EAPP from baseline were observed between treatment groups. The single observed case of moderate, probably drug-induced liver injury was the second case in the eliapixant phase 2 program conducted in the following indications: refractory or unexplained chronic cough, diabetic neuropathic pain, overactive bladder, and EAPP. Due to this, the benefit-risk ratio for the study was no longer considered to be positive.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT04614246; registered November 3, 2020.
Topics: Humans; Female; Endometriosis; Pelvic Pain; Adult; Double-Blind Method; Treatment Outcome; Middle Aged; Hydrocarbons, Fluorinated; Dose-Response Relationship, Drug; Pain Measurement; Pyrimidines
PubMed: 38890641
DOI: 10.1186/s12905-024-03188-8 -
The Journal of Headache and Pain Jun 2024Large conductance calcium-activated potassium (BK) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Large conductance calcium-activated potassium (BK) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BK channel opener) could induce migraine-like headache in persons with PPTH.
METHODS
This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period.
RESULTS
Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001).
CONCLUSIONS
Our results indicate that BK channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BK channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BK channel blockers in managing PPTH.
GOV IDENTIFIER
NCT05378074.
Topics: Humans; Female; Male; Adult; Double-Blind Method; Cross-Over Studies; Post-Traumatic Headache; Migraine Disorders; Middle Aged; Brain Concussion; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Young Adult; Large-Conductance Calcium-Activated Potassium Channels
PubMed: 38890563
DOI: 10.1186/s10194-024-01808-0 -
Nature Communications Jun 2024Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a... (Randomized Controlled Trial)
Randomized Controlled Trial
Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: a double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice.
Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419)).
Topics: Humans; Oryza; Feces; Female; Male; Double-Blind Method; Child; Micronutrients; Nutritional Status; Food, Fortified; Inflammation; Gastrointestinal Microbiome; Biomarkers; Adolescent; Vitamin A; Zinc
PubMed: 38890302
DOI: 10.1038/s41467-024-49093-4 -
Translational Psychiatry Jun 2024Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine's... (Randomized Controlled Trial)
Randomized Controlled Trial
Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine's antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes. Furthermore, the assessment of trait negative emotionality holds promise to link findings in healthy participants to potential AD mechanisms of ketamine. In this double-blind, placebo-controlled, randomized, single dose, parallel-group study, we collected resting-state fMRI data before, during, and 24 h after ketamine administration in a sample of 75 healthy male and female participants who were randomly allocated to one of three treatment conditions (ketamine, ketamine with lamotrigine pre- treatment, placebo). Spontaneous brain activity was extracted from two ventral and one dorsal subregions of the ACC. Our results showed activity decreases during the administration of ketamine in all three ACC subregions. However, only in the ventral subregions of the ACC this effect was attenuated by lamotrigine. 24 h after administration, ACC activity returned to baseline levels, but group differences were observed between the lamotrigine and the ketamine group. Trait negative emotionality was closely linked to activity changes in the subgenual ACC after ketamine administration. These results contribute to an understanding of the functional significance of ketamine effects in different subregions of the ACC by combining an approach to modulate glutamate release with the assessment of multiple timepoints and associations with trait negative emotionality in healthy participants.
Topics: Humans; Ketamine; Lamotrigine; Gyrus Cinguli; Male; Female; Double-Blind Method; Magnetic Resonance Imaging; Adult; Emotions; Young Adult; Antidepressive Agents; Excitatory Amino Acid Antagonists
PubMed: 38890270
DOI: 10.1038/s41398-024-02977-x