Integrated traditional Chinese and conventional medicine in the treatment of anemia due to lower-risk myelodysplastic syndrome: study protocol for a randomized placebo-controlled trial

Abstract Background Erythropoiesis and iron homeostasis are closely related; anemia due to lower-risk myelodysplastic syndromes (MDS) remains difficult to treat. In the last decade, we have been committed to improving the regulation of iron metabolism using traditional Chinese medicine (TCM). Previous studies have found that the TCM Yi Gong San (YGS) can reduce the expression of transferrin by inhibiting hepcidin overexpression caused by inflammation, promote the outward transfer of intracellular iron, and improve the symptoms of anemia. Here, our study aimed to compare the efficacy of a conventional drug with YGS with that of conventional medicine with placebo to provide a scientific basis for making clinical decisions. Methods A prospective, multicenter, double-blinded, randomized controlled clinical trial will be conducted to evaluate the therapeutic efficacy of conventional medicine combined with YGS with that of conventional medicine alone in the treatment of MDS. A total of 60 patients would be enrolled in this study, with each treatment group (conventional medicine + YGS and conventional medicine + placebo) comprising 30 patients. Oral medication would be administered twice daily for 3 months. All patients would be followed up throughout the 3-month period. The primary outcome was measured by assessing blood hemoglobin level. The secondary outcome was measured by assessing TCM symptom score, iron metabolism, hepcidin levels, and inflammatory factors. Discussion This trial would aim to demonstrate the effectiveness and feasibility of YGS in the treatment of lower-risk MDS anemia, as well as its impact on inflammatory factors and iron metabolism in patients with lower-risk MDS. Trial registration Chinese Clinical Trials Registry (http://www.chictr.org.cn/) ChiCTR1900026774. Registered on October 21, 2019.

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Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a community-based individually randomised controlled trial in Kasaï, Democratic Republic of Congo

BMJ Open ◽

10.1136/bmjopen-2020-041213 ◽

2020 ◽

Vol 10 (12) ◽

pp. e041213

Author(s):

Cécile Cazes ◽

Kevin Phelan ◽

Victoire Hubert ◽

Rodrigue Alitanou ◽

Harouna Boubacar ◽

...

Keyword(s):

Democratic Republic ◽

Democratic Republic Of Congo ◽

Controlled Trial ◽

Acute Malnutrition ◽

Secondary Outcome ◽

Controlled Clinical Trial ◽

Medical Complication ◽

Republic Of Congo ◽

Link Type ◽

Randomised Controlled

IntroductionAcute malnutrition (AM) is a continuum condition, arbitrarily divided into moderate and severe AM (SAM) categories, funded and managed in separate programmes under different protocols. Optimising acute MAlnutrition (OptiMA) treatment aims to simplify and optimise AM management by treating children with mid-upper arm circumference (MUAC) <125 mm or oedema with one product—ready-to-use therapeutic food—at a gradually tapered dose. Our main objective was to compare the OptiMA strategy with the standard nutritional protocol in children 6–59 months presenting with MUAC <125 mm or oedema without additional complications, as well as in children classified as uncomplicated SAM (ie, MUAC <115 mm or weight-for-height Z-score (WHZ) <−3 or with oedema).Methods and analysisThis study was a non-inferiority, individually randomised controlled clinical trial conducted at community level in the Democratic Republic of Congo. Children 6–59 months presenting with MUAC <125 mm or WHZ <−3 or with bipedal oedema and without medical complication were included after signed informed consent in outpatient health facilities. All participants were followed for 6 months. Success in both arms was defined at 6 months post inclusion as being alive, not acutely malnourished per the definition applied at inclusion and without an additional episode of AM throughout the 6-month observation period. Recovery among children with uncomplicated SAM was the main secondary outcome. For the primary objective, 890 participants were needed, and 480 children with SAM were needed for the main secondary objective. We will perform non-inferiority analyses in per-protocol and intention-to-treat basis for both outcomes.Ethics and disseminationEthics approvals were obtained from the National Health Ethics Committee of the Democratic Republic of Congo and from the Ethics Evaluation Committee of Inserm, the French National Institute for Health and Medical Research (Paris, France). We will submit results for publication to a peer-reviewed journal and disseminate findings in international and national conferences and meetings.Trial registration numberNCT03751475. Registered 19 September 2018, https://clinicaltrials.gov/ct2/show/NCT03751475.

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PEP-CoV protocol: a PEP flute-self-care randomised controlled trial to prevent respiratory deterioration and hospitalisation in early COVID-19

BMJ Open ◽

10.1136/bmjopen-2021-050582 ◽

2021 ◽

Vol 11 (6) ◽

pp. e050582

Author(s):

Annette Mollerup ◽

Sofus Christian Larsen ◽

Anita Selmer Bennetzen ◽

Marius Henriksen ◽

Mette Kildevaeld Simonsen ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Hospital Admission ◽

Usual Care ◽

Pulmonary Disease ◽

Controlled Trial ◽

Self Care ◽

Secondary Outcome ◽

Link Type ◽

Randomised Controlled ◽

At Home

IntroductionInfection with SARS-CoV-2 may progress to severe pulmonary disease, COVID-19. Currently, patients admitted to hospital because of COVID-19 have better prognosis than during the first period of the pandemic due to improved treatment. However, the overall societal susceptibility of being infected makes it pivotal to prevent severe courses of disease to avoid high mortality rates and collapse of the healthcare systems. Positive expiratory pressure (PEP) self-care is used in chronic pulmonary disease and has been shown to prevent pneumonia in a high-risk cohort of patients with leukaemia. PEP flute self-care to prevent respiratory deterioration and hospitalisation in early COVID-19: a randomised trial (The PEP-CoV trial) examines the effectiveness on respiratory symptoms and need of hospital admission by regular PEP flute use among non-hospitalised individuals with confirmed SARS-CoV-2 infection and COVID-19 symptoms.Methods and analysisIn this randomised controlled trial, we hypothesise that daily PEP flute usage as add-on to usual care is superior to usual care as regards symptom severity measured by the COPD Assessment Test (CAT) at 30-day follow-up (primary outcome) and hospital admission through register data (secondary outcome). We expect to recruit 400 individuals for the trial. Participants in the intervention group receive a kit of 2 PEP flutes and adequate resistances and access to instruction videos. A telephone hotline offers possible contact to a nurse. The eight-item CAT score measures cough, phlegm, chest tightness, dyspnoea, activities of daily living at home, feeling safe at home despite symptoms, sleep quality and vigour. The CAT score is measured daily in both intervention and control arms by surveys prompted through text messages.Ethics and disseminationThe study was registered prospectively at www.clinicaltrials.gov on 27 August 2020 (NCT04530435). Ethical approval was granted by the local health research ethics committee (Journal number: H-20035929) on 23 July 2020. Enrolment of participants began on 6 October 2020. Results will be published in scientific journals.Trial registration numberNCT04530435; Pre-results.

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The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05224-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Saeedeh Talebi ◽

Mahammad Safarian ◽

Mahmood Reza Jaafari ◽

Seyed Javad Sayedi ◽

Zahra Abbasi ◽

...

Keyword(s):

Cystic Fibrosis ◽

Controlled Trial ◽

Genetic Disorder ◽

The Body ◽

Inflammatory Factors ◽

Secondary Outcome ◽

Nasopharyngeal Swab ◽

Nutritional Strategy ◽

Cftr Protein ◽

The Impact

Abstract Background Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. Methods This prospective, double blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. Discussion Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. Trial registration Iranian Registry of Clinical Trials IRCT20200705048018N1. Registered on July 10, 2020.

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Effect of ‘hand and foot acupuncture with twelve needles’ on hemiplegia patients with ‘qi deficiency and blood stasis’ syndrome in the convalescent stage of Ischaemic stroke: study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-021-05128-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wei-Hao Fang ◽

Gui-Ling Wang ◽

Qiang Liu ◽

Xiao Ding ◽

Zhen-Yao Wang ◽

...

Keyword(s):

Ischaemic Stroke ◽

Controlled Trial ◽

Blood Stasis ◽

Blood Stasis Syndrome ◽

Controlled Clinical Trial ◽

Link Type ◽

Stroke Study ◽

Group A ◽

Randomised Controlled ◽

Convalescent Stage

Abstract Background Hemiplegia is a common sequela after stroke, and acupuncture is one of the most common physical therapies used to treat hemiplegia during the recovery stage after ischaemic stroke. ‘Hand and foot acupuncture with twelve needles’ is an acupuncture treatment performed after stroke. The principal objective of this study is to assess the efficacy and safety of ‘hand and foot acupuncture with twelve needles’ for hemiplegia in the convalescent stage of ischaemic stroke. Methods This is the protocol for a randomised, controlled clinical trial with two groups: a ‘hand and foot acupuncture with twelve needles’ group and a routine acupuncture group. A total of 208 participants will be randomly assigned to two different groups in a 1:1 ratio and will undergo conventional rehabilitation. Limb function will be evaluated by the simplified Fugl-Meyer assessment scale, Barthel Index, modified Ashworth scale and National Institute of Health stroke scale. The participants will be evaluated at baseline (on the day of enrolment) and followed up at 2 weeks, 1 month, 2 months and 3 months after enrolment. Discussion The results of this study will provide evidence on the effectiveness of ‘hand and foot acupuncture with twelve needles’ in the treatment of limb dysfunction that can be used for future evaluations. Trial registration Chictr.org.cnChiCTR1900021774. Registered on 8 March 2019

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Efficacy of Chinese Herbal Medicine Jiangniaosuan Formula for Treatment of Hyperuricemia: Study Protocol For A Double-Blinded Non-Inferiority Randomized Controlled Clinical Trial

10.21203/rs.3.rs-707319/v1 ◽

2021 ◽

Author(s):

Yafang Guo ◽

Hong Lu ◽

Jing Gan ◽

Dongdong Li ◽

Jiandong Gao ◽

...

Keyword(s):

Herbal Medicine ◽

Chinese Herbal Medicine ◽

Serum Uric Acid Level ◽

Controlled Trial ◽

Secondary Outcome ◽

Controlled Clinical Trial ◽

Randomized Controlled ◽

Chinese Herbal ◽

To Receive ◽

Be The Change

Abstract Background: Jiangniaosuan formula (JNSF) is commonly used in China for treating hyperuricemia, but there is little research-based evidence to support its use. This randomized controlled trial aims to assess the efficacy and safety of JNSF.Methods: A total of 72 patients with hyperuricemia will be selected and randomly assigned in a ratio of 1:2 to receive either Western medicine i.e., febuxostat 40 mg (WG group; n = 24) or Chinese herbal medicine group, i.e., Jiangniaosuan formula + febuxostat 20 mg (WJNSG; n = 48). After 12 weeks, the WJNSG will be randomly divided into two groups of 24 patients each; one group (WJNSG; n = 24)still will receive febuxostat 20 mg + Jiangniaosuan formula and the other group(JNSG; n = 24) will continue to receive Jiangniaosuan formula+Placebo. Participants will be followed up at 4-week intervals. The primary outcome will be the change in serum uric acid level, and the secondary outcome will be the change in Traditional Chinese Medicine (TCM) syndrome scores. Serum creatinine, blood glucose, and insulin levels will also be measured.Discussion: We hypothesize that patients with hyperuricemia will benefit from JNSF. This study will provide evidence-based recommendations for clinicians.Dissemination: The results will be published in a peer-reviewed journal and disseminated by academic conferences.Trial registration : This trial is registered with ClinicalTrials.gov, number ChiCTR2000041083. 22 Registered on 3 May 2021.

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Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke

Neurology ◽

10.1212/wnl.0000000000011440 ◽

2021 ◽

pp. 10.1212/WNL.0000000000011440

Author(s):

Jong-Won Chung ◽

Won Hyuk Chang ◽

Oh Young Bang ◽

Gyeong Joon Moon ◽

Suk Jae Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Controlled Trial ◽

Outcome Evaluation ◽

Autologous Serum ◽

Secondary Outcome ◽

Control Group ◽

Link Type ◽

Significant Difference ◽

Major Stroke

ObjectiveTo test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.MethodsIn this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.ResultsA total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range, 28–83) years, and mean interval between stroke onset to randomization was 20.2 (range, 5–89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious, treatment-related adverse events.ConclusionsIntravenous application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.Classification of evidenceThis study provides Class III evidence that autologous mesenchymal stem cells do not improve 90-day outcomes in patients with chronic stroke.Trial registrationclinicaltrials.gov Identifier: NCT01716481.

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Thunder-fire moxibustion for cervical spondylotic radiculopathy: Study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-019-4012-1 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Yunxuan Huang ◽

Jiabi Zhang ◽

Buhui Xiong ◽

Ruina Huang ◽

Wenjing Zhao ◽

...

Keyword(s):

Short Form ◽

Controlled Trial ◽

Neck Disability Index ◽

Life Assessment ◽

Secondary Outcome ◽

Mcgill Pain Questionnaire ◽

Social Evaluation ◽

Clinical Trial Registry ◽

Link Type ◽

Cervical Spondylotic Radiculopathy

Abstract Background Thunder-fire moxibustion originated in China and contains traditional Chinese medicine. It can produce strong firepower, infrared thermal radiation, and medicinal effects when burning on the acupoints. Thunder-fire moxibustion is commonly used in patients with neck pain, but its efficacy has rarely been systematically demonstrated. We designed a randomized trial of thunder-fire moxibustion on cervical spondylotic radiculopathy (CSR) to investigate whether it is more effective than ibuprofen sustained-release capsules. Methods One hundred patients will be recruited and randomly divided into thunder-fire moxibustion and ibuprofen groups. The intervention consists of ten treatments and will last for 2 weeks. The Yasuhisa Tanaka 20 Score Scale is used as the primary outcome measure. It contains a combination of the self-conscious symptom in patients, objective clinical evaluation from doctors, and social evaluation (the ability to work and live). The objective and comprehensive evaluation of CSR patients before and after treatment is particularly needed. The Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), Neck Disability Index score scale (NDI), and the Quality of Life Assessment (SF-36) are applied as secondary outcome measures. The assessment will take place at the baseline and the first and second weekends of treatment. If an adverse event (AEs) occurs, it will be reported. Discussion The aim of this trial is to determine whether thunder-fire moxibustion is more effective than ibuprofen in the treatment of patients with CSR. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR1800018820. Registered on 11 October 2018.

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A multicenter, randomized, active-controlled, clinical trial study to evaluate the efficacy and safety of navigation guided balloon Eustachian tuboplasty

Scientific Reports ◽

10.1038/s41598-021-02848-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sung-Won Choi ◽

Se-Joon Oh ◽

Yehree Kim ◽

Min Young Kwak ◽

Myung-Whan Suh ◽

...

Keyword(s):

Eustachian Tube ◽

Valsalva Maneuver ◽

Controlled Trial ◽

Pure Tone Audiometry ◽

Secondary Outcome ◽

Control Group ◽

Controlled Clinical Trial ◽

Multicenter Rct ◽

Balloon Eustachian Tuboplasty

AbstractTo assess the safety and efficacy of navigation-guided balloon Eustachian tuboplasty (BET) compared to medical management (MM) alone in patients with chronic Eustachian tube dilatory dysfunction (ETD). This is a prospective, multicenter, 1:1 parallel-group, randomized controlled trial (RCT). It aims to assess the efficacy of navigation-guided BET compared to MM alone in patients with chronic ETD. The primary outcome measure was an improvement in the Eustachian tube dysfunction questionnaire (ETDQ)-7 score at the 6-week follow-up compared with baseline. Secondary outcome measures included changes in the signs and symptoms during the follow-up, changes in the score for each subcategory of ETDQ-7, type of tympanometry, pure tone audiometry, and the availability of a positive modified Valsalva maneuver. Navigation-guided BET was safely performed in all patients. A total of 38 ears of 31 patients (19 ears of 16 patients in the BET group and 19 ears of 15 patients in the control group) completed the planned treatment and 6 weeks of follow-up. More patients in the BET group (1.99 ± 0.85) had less symptomatic dysfunction than in the control group (3.40 ± 1.29) at 6 weeks post-procedure (P = 0.001). More patients experienced tympanogram improvement in the BET group at 6 weeks compared to the control group (36.5% vs. 15.8%) with a positive modified Valsalva maneuver (36.6% vs. 15.8%, P = 0.014). Additionally, air–bone gap change was significantly decreased in the BET group compared to the control group at the 6-week follow-up visit (P = 0.037). This prospective, multicenter, RCT study suggests that navigation-guided BET is a safe and superior treatment option compared to MM alone in patients with chronic ETD.

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Efficacy and safety of Xiaoyao pills for mild to moderate depression: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05909-y ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Zhe Xue ◽

Zhen Huang ◽

Shu-li Cheng ◽

Xi-hong Wang ◽

Xuan Zhou ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Adverse Reactions ◽

Controlled Trial ◽

Depression Scale ◽

Secondary Outcome ◽

Controlled Clinical Trial ◽

Hamilton Depression Scale ◽

Efficacy And Safety ◽

Moderate Depression

Abstract Background Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients. Methods This study is a multi-centre, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants are assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline (before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks. Discussion The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency. Trial registration ClinicalTrials.gov ISRCTN12746343. Registered on September 25, 2020.

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Iron-Response Element Binding to Iron Regulatory Protein (IRP) 1 and 2 Are Indispensable for Adipose Tissue Browning

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_041 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1283-1283

Author(s):

Mikyoung You ◽

Soonkyu Chung

Keyword(s):

Adipose Tissue ◽

Iron Metabolism ◽

Knockout Mice ◽

Iron Homeostasis ◽

Regulatory Protein ◽

Mrna Translation ◽

Intracellular Iron ◽

Mobility Shift ◽

Iron Regulatory Proteins ◽

Tissue Browning

Abstract Objectives Intracellular iron homeostasis is tightly regulated in posttranscriptional levels via iron regulatory proteins (IRPs). IRPs bind to the iron-responsive elements (IREs), leading to either mRNA translation or stability. Our recent study demonstrated that iron metabolism is intimately linked with adipose tissue browning and thermogenic activation. However, the role of IRP/IRE interactions in the adipose tissue is poorly understood. We aim to characterize the IRP/IRE interactions in the adipose tissue in terms of depot-specificity and thermogenic potential. Methods To induce adipocyte browning, mice were administrated with beta-3 adrenoceptor agonist CL316243 (CL) for 5 days, and different depots of adipose tissue of epididymal (eWAT), inguinal (iWAT), brown (BAT), and liver were collected. Iron metabolism and thermogenesis were evaluated. To investigate the IRP/IRE binding, electrophoretic mobility shift assay (EMSA) was performed in the cytosolic using the fluorescence-labeled IRE (IR-IRE). To distinguish the IRE binding with IRP1 and 2, the cytosolic fraction from IRP1 and 2 knockout mice were used as positive controls. Results In a normal temperature, the constitutive IRP/IRE binding was found in the BAT, but not in the eWAT and iWAT. In response to CL treatment, iron content and transferrin receptor levels significantly increased in the WAT. Accordingly, the IRE/IRPs binding significantly increased in the CL-treated iWAT. Genetic deletion of IRP1 or 2 poses a marginal impact on constitutively active BAT development, suggesting IRP1 and 2 plays a compensatory role. Unlikely to BAT, the deletion of either IRP1 or 2 failed to induce WAT browning in the IRP1 and 2 knockout mice with CL stimulation. Consistently, both IRE binding to IRP1 and 2 were manifest in the CL treated iWAT, implicating that IRP1 and 2 plays a separate and synergistic function for WAT browning. Conclusions Our study defined the depot-specific iron regulatory metabolism in the adipose tissue using an innovative EMSA method. We demonstrated that, for the first time in our knowledge, IRE binding to both IRP1 and IRP2 is indispensable for the thermogenic activation of WAT, which is distinct from the iron regulatory mechanism found in the BAT. We propose that iron metabolism in the WAT is a novel determinant for WAT browning and thermogenic energy expenditure. Funding Sources None.

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