Co-Administration of Iron and a Bioavailable Curcumin Supplement Increases Serum BDNF Levels in Healthy Adults

Brain-derived neurotrophic factor (BDNF) is key for the maintenance of normal neuronal function and energy homeostasis and has been suggested to improve cognitive function, including learning and memory. Iron and the antioxidant curcumin have been shown to influence BDNF homeostasis. This 6-week, double blind, randomized, placebo-controlled study examined the effects of oral iron supplementation at low (18 mg) and high (65 mg) ferrous (FS) iron dosages, compared to a combination of these iron doses with a bioavailable formulated form of curcumin (HydroCurcTM; 500 mg) on BDNF levels in a healthy adult cohort of 155 male (26.42 years ± 0.55) and female (25.82 years ± 0.54) participants. Participants were randomly allocated to five different treatment groups: both iron and curcumin placebo (FS0+Plac), low dose iron and curcumin placebo (FS18+Plac), low dose iron and curcumin (FS18+Curc), high dose iron and curcumin placebo (FS65+Plac) and high dose iron and curcumin (FS65+Curc). Results showed a significant increase in BDNF over time (26%) in the FS18+Curc group (p = 0.024), and at end-point between FS18+Curc and FS18+Plac groups (35%, p = 0.042), demonstrating for the first time that the combination with curcumin, rather than iron supplementation alone, results in increased serum BDNF. The addition of curcumin to iron supplementation may therefore provide a novel approach to further enhance the benefits associated with increased BDNF levels.

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SUN-042 Low Dose Cyproterone Acetate for the Treatment of Transgender Women - a Retrospective Study

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1412 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Naomi Even-Zohar ◽

Yael Sofer ◽

Iris Yaish ◽

Merav Serebro ◽

Karen Tordjman ◽

...

Keyword(s):

Cyproterone Acetate ◽

Dose Group ◽

Low Dose ◽

Dose Range ◽

Hormonal Treatment ◽

Transgender Women ◽

High Dose ◽

Historical Cohort ◽

Treatment Groups ◽

First Time

Abstract Introduction : Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (<20 mg/day), compared with high dose (>50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.

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Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Recombinant Human Intestinal Trefoil Factor Oral Spray for Prevention of Oral Mucositis in Patients With Colorectal Cancer Who Are Receiving Fluorouracil-Based Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2008.21.2381 ◽

2009 ◽

Vol 27 (26) ◽

pp. 4333-4338 ◽

Cited By ~ 43

Author(s):

Douglas E. Peterson ◽

Nicholas P. Barker ◽

Lilia I. Akhmadullina ◽

Irina Rodionova ◽

Nailya Z. Sherman ◽

...

Keyword(s):

Colorectal Cancer ◽

Oral Mucositis ◽

Low Dose ◽

Area Under The Curve ◽

Controlled Study ◽

High Dose ◽

Trefoil Factor ◽

Intestinal Trefoil Factor ◽

Double Blind ◽

Who Grade

Purpose This study evaluated the safety and efficacy of recombinant human intestinal trefoil factor (rhITF) administered as topical oral spray for prevention and treatment of chemotherapy-induced oral mucositis (OM). Patients and Methods Ninety-nine patients with colorectal cancer who had moderate to severe OM (WHO grade ≥ 2) in the first cycle of chemotherapy were randomly assigned to receive either placebo, rhITF 10 mg/mL (ie, low dose), or rhITF 80 mg/mL (ie, high dose) by oral spray (300 μL, eight times each day) for 14 consecutive days in the second chemotherapy cycle. Patients were assessed on days 1, 3, 5, 7, 10, 12, 14, and 21 (± 2 days for the last assessment) for safety and for OM incidence and severity. Results Treatment of patients at high risk for developing OM with low- or high-dose rhITF significantly reduced the amount of incidence (75% to 81%; low-dose rhITF P < .001; high-dose rhITF P = .002). Frequencies of WHO grade ≥ 2 OM in the placebo, low-dose rhITF, and high-dose rhITF groups were 48.5%, 9.1%, and 12.1%, respectively. Assessment of the area under the curve revealed statistically significant reductions in OM severity in the rhITF-treated groups versus placebo. Only a minority of patients (6.1%) reported treatment-emergent adverse events (TEAEs), all of which were mild to moderate in intensity and resolved without sequelae. The incidence of TEAEs was not significantly different among treatment groups. Conclusion rhITF oral spray formulation was safe and effective when used for the reduction of chemotherapy-associated OM in patients with colorectal cancer. Patients exhibited high compliance in dosing administration. Future clinical study is planned to develop this drug for use in OM management in patients with cancer.

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A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study

Frontiers in Nutrition ◽

10.3389/fnut.2021.658630 ◽

2021 ◽

Vol 8 ◽

Author(s):

Juntao Kan ◽

Junrui Cheng ◽

Chun Hu ◽

Liang Chen ◽

Siyu Liu ◽

...

Keyword(s):

Clinical Trial ◽

Lactic Acid ◽

Chronic Fatigue Syndrome ◽

Low Dose ◽

Chronic Fatigue ◽

High Dose ◽

Physical Fatigue ◽

Double Blind ◽

Treatment Groups ◽

Fatigue Syndrome

Dietary therapy may be beneficial in alleviating symptoms of chronic fatigue syndrome (CFS), a disorder that is characterized by extreme fatigue and other symptoms, but the cause of which remains unclear. The aim of this study was to evaluate the protective effect of a botanical product containing cistanche (Cistanche tubulosa [Schenk] Wight) and ginkgo (Ginkgo biloba L.) extracts on adults with CFS in a randomized, double-blind, placebo-controlled clinical trial. A total of 190 subjects (35–60 years old, non-obese) with CFS were randomized to receive one tablet of a low dose (120-mg ginkgo and 300-mg cistanche), a high dose (180-mg ginkgo and 450-mg cistanche) or a placebo once daily for 60 days. Blood samples and responses on the Chalder fatigue scale (CFQ 11), the World Health Organization's quality of life questionnaire (WHOQOL), and the sexual life quality questionnaire (SLQQ) were collected at baseline and post-intervention. CFS symptoms of impaired memory or concentration, physical fatigue, unrefreshing sleep, and post-exertional malaise were significantly improved (p < 0.001) in both of the treatment groups. The botanical intervention significantly decreased physical and mental fatigue scores of CFQ 11 and improved WHOQOL and SLQQ scores of the subjects (p < 0.01). Levels of blood ammonia and lactic acid in the treatment groups were significantly lower than those of the placebo group (low-dose: p < 0.05; high-dose: p < 0.01). In addition, the change in lactic acid concentration was negatively associated with the severity of CFS symptoms (p = 0.0108) and was correlated with the change in total physical fatigue score of the CFQ (p = 0.0302). Considering the trivial effect size, the results may lack clinical significance. In conclusion, this botanical product showed promising effects in ameliorating the symptoms of CFS. Clinical trials with improved assessment tools, an expanded sample size, and an extended follow-up period are warranted to further validate the findings.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT02807649.

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Vardenafil demonstrates first-dose success and reliability of penetration and maintenance of erection in men with erectile dysfunction — RELY-II

Canadian Urological Association Journal ◽

10.5489/cuaj.590 ◽

2013 ◽

Vol 2 (3) ◽

pp. 187 ◽

Cited By ~ 12

Author(s):

Luc Valiquette ◽

Francesco Montorsi ◽

Stephen Auerbach

Keyword(s):

Erectile Dysfunction ◽

Nasal Congestion ◽

Treatment Phase ◽

Patient Characteristics ◽

Controlled Study ◽

Repeat Dose ◽

Open Label ◽

Double Blind ◽

Treatment Groups ◽

First Time

Objective: Vardenafil has been shown to be efficacious in patients with erectile dysfunction (ED). We evaluated first-dose and repeat-dose response to vardenafil 20 mg.Methods: This randomized, placebo-controlled study consisted of a 4-week, treatment-free run-in phase; a 1-week, open-label challenge phase; and a 12-week, double-blind treatment phase. Primary efficacy was assessed in terms of reliability of insertion based on dose as measured by the Sexual Encounter Profile question 2 (SEP2). We assessed safety by evaluating adverse events (AEs).Results: Baseline patient characteristics in the 2 treatment groups were similar. The most common comorbidities were hypertension (41%), dyslipidemia (28%) and diabetes mellitus (24%). Of the 573 patients receiving the 20-mg vardenafil challenge dose, 464 (81%) achieved first-time successful penetration (SEP2), and 401 (70%) reported successful erection maintenance (SEP3). Patients receiving vardenafil 20 mg had statistically (p < 0.001) and clinically superior SEP2 rates (85%) through weeks 0–12, compared with patients receiving placebo (45%). The increase in reliability of insertion was seen within the first 4 weeks of treatment. Vardenafil therapy was statistically (p < 0.001) and clinically superior to placebo for all secondary efficacy end points as well. Most AEs associated with vardenafil were mild to moderate, with headache, flushing and nasal congestion most frequently reported.Conclusion: Vardenafil 20 mg had a high first-dose success rate for both SEP2 (81%) and SEP3 (70%); this was maintained through to the study end point (85% for SEP2 and 78% for SEP3). These findings were achieved in men with frequentlyassociated comorbidities including hypertension, dyslipidemia and diabetes.

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SM03, an anti-human CD22 monoclonal antibody, for active rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled study

Rheumatology ◽

10.1093/rheumatology/keab699 ◽

2021 ◽

Author(s):

Jing Li ◽

Mengtao Li ◽

Di Wu ◽

Jiaxin Zhou ◽

Shui-on Leung ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Dose Group ◽

Low Dose ◽

Response Rate ◽

Controlled Study ◽

High Dose ◽

Double Blind ◽

Acr20 Response ◽

Acr20 Response Rate

Abstract Objective SM03, a novel chimaeric mAb specific to B cell-restricted antigen CD22, has been developed to treat RA and other B-cell-related diseases. This 24-week phase II randomized, double-blind, multi-dose, placebo-controlled study aimed to evaluate the efficacy and safety of SM03 in moderately-to-severely active RA patients in China. Methods One hundred and fifty-six patients on background MTX were randomized in a 1:1:1 ratio to receive a cumulative dose of 3600 mg (high dose, 600 mg × 6 infusions at weeks 0, 2, 4, 12, 14 and 16) or 2400 mg SM03 (low dose, 600 mg × 4 infusions at weeks 0, 2, 12 and 14) or the placebo. The primary outcome was the 24-week ACR 20% improvement criteria (ACR20) response rate. Safety was also assessed. Results The 24-week ACR20 response rate was significantly higher with high- (65.3%, P = 0.002) and low-dose SM03 (56.9%, P = 0.024) than with placebo (34.0%), but comparable between the high- and low-dose group. The rate of adverse events was not statistically different among the high-dose group (35.3%), the low-dose group (51.9%) and the placebo group (34.6%). Thirteen (12.6%) patients receiving SM03 reported treatment-emergent infections, including 3.9% patients in the high-dose group. No patients reported severe treatment-emergent infections or malignancies. Conclusions In active RA Chinese patients receiving background MTX, SM03 at a cumulative dose of both 2400 mg and 3600 mg is efficacious and well-tolerated throughout the 24 weeks of treatment. Moreover, SM03 has demonstrated a good safety profile. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT04192617.

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146 Efficacy and Safety of the Asenapine Transdermal Patch, HP-3070, for Schizophrenia: A Phase 3, Randomized, Placebo-Controlled, Inpatient Study

CNS Spectrums ◽

10.1017/s1092852920000620 ◽

2020 ◽

Vol 25 (2) ◽

pp. 293-293 ◽

Cited By ~ 1

Author(s):

Leslie Citrome ◽

David Walling ◽

Courtney Zeni ◽

Marina Komaroff ◽

Alexandra Park

Keyword(s):

Low Dose ◽

Vital Signs ◽

Severity Of Illness ◽

Application Site ◽

High Dose ◽

Phase 3 ◽

Double Blind ◽

Treatment Groups ◽

Treatment Comparison ◽

The Us

Abstract:Background:Asenapine is a 2nd-generation antipsychotic currently marketed as a sublingual (SL) tablet in the US for the treatment of schizophrenia. HP-3070, asenapine transdermal system, is a patch for treatment of schizophrenia in adults. Low- and high- HP-3070 doses deliver asenapine concentrations that are similar to SL asenapine 5 mg BID and 10 mg BID, respectively, but with fewer peak and trough fluctuations.Methods:In this Phase 3, randomized, double-blind, placebo (PBO)-controlled, 6-week inpatient study, adults with schizophrenia having baseline Positive and Negative Syndrome Scale (PANSS) total score ≥80 and Clinical Global Impression–Severity of Illness Scale (CGI-S) score ≥4 were randomized 1:1:1 to HP 3070 high-dose, HP-3070 low-dose, or PBO.The primary efficacy objective was Week 6 PANSS score change from baseline (CFB) vs PBO.The key secondary objective was Week 6 CGI-S CFB vs PBO. Safety assessments included treatment-emergent adverse events (TEAEs), laboratory results, vital signs, dermal safety, and extrapyramidal symptoms (EPS) assessments.Results:A total of 616 patients were randomized, with 486 patients completing the study. Discontinuation rates were 23.3%, 18.6%, and 21.4% for HP-3070 high-dose, HP-3070 low-dose, and PBO, respectively; withdrawal of consent and AEs were the most common reasons for discontinuation. Demographics and baseline characteristics were well-balanced among treatment groups.For PANSS total score, least squares mean (LSM) (standard error [SE]) estimates of the treatment comparison (HP-3070 vs PBO) for CFB at Week 6 were -4.8 (1.634; 95% CI: -8.06, -1.64; p=0.003) and -6.6 (1.630; 95% CI: 9.81, 3.40; p<0.001) for HP-3070 high- and low-dose, respectively. For CGI-S CFB at Week 6, LSM (SE) for the treatment comparison were 0.4 (0.100; 95% CI: 0.55, 0.16; p<0.001) for HP 3070 high-dose and 0.4 (0.099; 95% CI: 0.64, 0.25; p<0.001) for low-dose.No deaths or serious TEAEs related to study treatment occurred. The HP-3070 safety profile was consistent with SL asenapine. Incidence of TEAEs at the patch application site was higher for HP-3070 (14.2% high-dose, 15.2% low-dose) than for PBO (4.4%); most of these events were mild or moderate in severity. PBO patients had higher rates of psychiatric disorders (24.3% vs 15.7% and 17.6% for HP-3070 high- and low-dose, respectively), with insomnia and anxiety as most common. Study treatment discontinuations due to application site reactions or skin disorders were low (≤0.5%) across treatment groups. There was no marked mean CFB for vital signs or electrocardiogram parameters, nor treatment differences observed on EPS assessments.Conclusions:In this study, HP-3070 was efficacious, safe, and well-tolerated for treating schizophrenia in adults; both doses met primary and key secondary endpoints. As the first transdermal antipsychotic patch in the US, HP-3070 will provide patients a novel treatment option.Funding Acknowledgements:Funded by Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical Co.

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Use of single-dose oral gabapentin to attenuate fear responses in cage-trap confined community cats: a double-blind, placebo-controlled field trial

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x17719399 ◽

2017 ◽

Vol 20 (6) ◽

pp. 535-543 ◽

Cited By ~ 20

Author(s):

Katherine E Pankratz ◽

Kelli K Ferris ◽

Emily H Griffith ◽

Barbara L Sherman

Keyword(s):

Single Dose ◽

Controlled Study ◽

High Dose ◽

Inclusion Criteria ◽

Double Blind ◽

Double Blind Placebo ◽

Facial Injuries ◽

Treatment Groups ◽

Dose Oral ◽

Sedation Scores

Objectives This double-blind, placebo-controlled study evaluated the safety and efficacy of single-dose oral gabapentin administered for the attenuation of fear responses in cage-trap confined community cats. Methods Community cats presented in cage traps for trap–neuter–return (TNR) were recruited and screened for inclusion. Each enrolled cat was randomly assigned and administered one of three equal-volume, single-dose treatments: placebo, low-dose gabapentin (50 mg) or high-dose gabapentin (100 mg). At baseline, 1, 2, 3 and 12 h post-administration, a single, blinded observer scored each cat for signs of fear and sedation using published paradigms, calculated the respiratory rate and documented any observable facial injuries. Results Fifty-three cats met the inclusion criteria and completed the study. Cat stress score (a measure of fear) was lower in cats that received gabapentin (50 or 100 mg) than in cats that received placebo (50 mg: P = 0.027; 100 mg: P = 0.029), with the greatest reduction at 2 h post-treatment ( P = 0.0007). Respiratory rates did not differ between treatment groups. There was no difference in sedation scores between the groups ( P = 0.86) at any time point ( P = 0.09). Cat facial injuries did not vary by treatment group or over time. No adverse effects were detected specific to gabapentin administration. At 1 h, hypersalivation was observed in four cats across all treatment groups. All cats recovered from surgery and anesthesia uneventfully. Conclusions and relevance This study supports the hypothesis that 50 mg or 100 mg gabapentin (9.2–47.6 mg/kg per cat) reduces fear responses in confined community cats without measurable sedation over 3 h post-administration vs placebo. Gabapentin treatment was well tolerated in this population of cats. Further studies are recommended to investigate the use of oral gabapentin earlier in the TNR process, such as immediately after trapping or prior to transport for the prevention of confinement-related injuries.

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Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159539 ◽

1990 ◽

Vol 48 (3) ◽

pp. 398-399

Author(s):

A.M. Andrews ◽

S.W. Wilson ◽

A.C. Scallet ◽

S.F. Ali ◽

J. Bailey ◽

...

Keyword(s):

Synaptic Vesicles ◽

Rhesus Monkeys ◽

Low Dose ◽

Inhalation Exposure ◽

Synaptic Cleft ◽

High Dose ◽

Withdrawal Time ◽

Treatment Groups ◽

Ultrastructural Evidence ◽

Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

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SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9i5.13237 ◽

2016 ◽

Vol 9 (5) ◽

pp. 197

Author(s):

Meilinah Hidayat ◽

Sijani Prahastuti ◽

Estherolita Dewi ◽

Dewi Safitri ◽

Siti Farah Rahmawati ◽

...

Keyword(s):

Liver Function ◽

Toxicity Test ◽

Low Dose ◽

Ethanol Extract ◽

Good Effect ◽

Control Group ◽

High Dose ◽

Subchronic Toxicity ◽

Treatment Groups ◽

Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

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