Reversal of Epigenetic Age with Diet and Lifestyle in a Pilot Randomized Clinical Trial

Manipulations to set back biological age and extend lifespan in animal models are well established, and translation to humans has begun. The length of human life makes it impractical to evaluate results by plotting mortality curves, so surrogate markers of age have been suggested and, at present, the best established surrogates are DNA methylation clocks. Herein we report on a randomized, controlled clinical trial designed to be a first step in evaluating the effect of a diet and lifestyle intervention on biological age. Compared to participants in the control group (n=20), participants in the treatment group tested an average 3.23 years younger at the end of the eight-week program according to the Horvath DNAmAge clock (p=0.018). Those in the treatment group (n=18) tested an average 1.96 years younger at the end of the program compared to the same individuals at the beginning with a strong trend towards significance (p=0.066 for within group change). This is the first such trial to demonstrate a potential reversal of biological age. In this study, the intervention was confined to diet and lifestyle changes previously identified as safe to use. The prescribed program included multiple components with documented mechanistic activity on epigenetic pathways, including moderate exercise, breathing exercises for stress, and a diet rich in methyl donor nutrients and polyphenols.

Download Full-text

Efficacy of microcurrent therapy for treatment of acute knee pain: A randomized double-blinded controlled clinical trial

Clinical Rehabilitation ◽

10.1177/0269215520965320 ◽

2020 ◽

pp. 026921552096532

Author(s):

Daryl Lawson ◽

Kevin H Lee ◽

Hyun Bin Kang ◽

Nan Yang ◽

Tracy Llewellyn ◽

...

Keyword(s):

Clinical Trial ◽

Treatment Group ◽

Knee Pain ◽

Rating Scale ◽

Short Form ◽

Control Group ◽

Controlled Clinical Trial ◽

Physical Function Score ◽

Double Blinded ◽

Acute Knee

Objective: We would like to determine whether electrotherapy, specifically microcurrent therapy, increases function and decreases pain in people who have acute knee pain. Design: Randomized, double-blinded, placebo-controlled clinical trial. Setting: University laboratory and patient home. Subjects: A total of 52 subjects (35 females and 17 males) with acute knee pain. Intervention: Treatment group ( n = 26) wore the active microcurrent therapy device at home for 3 hours per day for 4 weeks and the control group ( n = 26) wore the placebo for 3 hours per day for 4 weeks. Main Measures: Numeric Pain Rating Scale (NPRS) and Short Form 12 (SF-12) health scale were used to measure the pain level and the functionality of the participants. Secondary assessments included musculoskeletal ultrasound imaging (MSK US) and Lower Extremity Functional Scale (LEFS). Results: A total of 52 subjects completed the study; 26 in the treatment group and 26 in the control group. Microcurrent therapy significantly reduced pain over 4 weeks. Especially week three was significant ( P < 0.01) after adjusting for the family-wise error rate. The analysis on SF-12 revealed those with microcurrent therapy showed an increasing trend in the improvement of physical function score until week three. Conclusion: An active microcurrent therapy device decreased knee pain and increased function. Microcurrent therapy may be an alternative or used with a pharmacological approach for people with acute knee pain.

Download Full-text

Traditional Chinese Medicine in Patients With Primary Sjogren's Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Frontiers in Medicine ◽

10.3389/fmed.2021.744194 ◽

2021 ◽

Vol 8 ◽

Author(s):

Huang-Hsi Chen ◽

Jung-Nien Lai ◽

Min-Chien Yu ◽

Chia-Yin Chen ◽

Yi-Ting Hsieh ◽

...

Keyword(s):

Clinical Trial ◽

Placebo Group ◽

Treatment Group ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Control Group ◽

Controlled Clinical Trial ◽

Sjögren‘S Syndrome

Background: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease mainly characterized by dryness, fatigue, and pain. Current therapies for SS in Western medicine are limited. The purpose of this clinical study was to explore the efficacy and safety of using a traditional Chinese medicine (TCM) formula on patients with primary SS.Methods: We performed a 12-week, randomized, double-blinded, placebo-controlled clinical trial at Chung Shan Medical University Hospital. We included 42 patients with SS between the ages of 20 and 80 years who met the classification criteria of the American and European Consensus Group (AECG). Patients who had other severe systemic manifestations or diseases were excluded from this trial. After screening, patients were randomly assigned to the TCM treatment group or placebo group (ratio of 2:1). We treated the TCM group with 6 g of Gan-Lu-Yin granules after breakfast and 6 g of Jia-Wei-Xiao-Yao-San combined with 1 g of Suan-Zao-Ren-Tang and 1 g of Ye-Jiao-Teng every night after dinner. Patients in the control group were treated with a placebo with the same appearance and flavor but only one-tenth the dosage of that received by the treatment group. The European League Against Rheumatism Sjogren's Syndrome Patient-Reported Index (ESSPRI) was used as the primary endpoint at week 12. Secondary endpoints were the Sjogren's Syndrome Disease Activity Index (SSDAI), physician global assessment (PGA), visual analogue scale (VAS), Multidimensional Fatigue Inventory, Medical Outcomes Survey Short Form-36, and the Pittsburgh Sleep Quality Score (PSQI). Adverse events were also recorded.Results: Of the 42 randomized patients, 28 patients were assigned to the TCM treatment group and 14 patients were assigned to the controlled group. During the study period, 5 patients withdrew from the TCM group and 7 withdrew from the control group. At week 12, the ESSPRI scores of both groups had improved. The ESSPRI score of the treatment group decreased by 0.62 (95% CI P = 0.557) and that of the placebo group decreased by 0.91 (P = 0.557). However, no significant difference was observed between the two groups. Sleep duration in the PSQI was −0.61, which exhibited an improvement of more than the −0.21 compared with the placebo group (P = 0.914).Conclusion: At week 12, the ESSPRI scores did not reveal that the use of the TCM formula was efficacious for treating patients with Sjogren's syndrome. However, the PSQI scores indicated that this formula could prolong patient sleep duration. We also found that this formula could decrease the blood pressure of patients.

Download Full-text

The control of pain due to dentin hypersensitivity in individuals with molar–incisor hypomineralisation: a protocol for a randomised controlled clinical trial

BMJ Open ◽

10.1136/bmjopen-2020-044653 ◽

2021 ◽

Vol 11 (3) ◽

pp. e044653

Author(s):

Ana Paula Taboada Sobral ◽

Elaine Marcilio Santos ◽

Ana Cecilia Aranha ◽

Paulo Vinícius Soares ◽

Caroline Moraes Moriyama ◽

...

Keyword(s):

Clinical Trial ◽

Tooth Enamel ◽

Control Group ◽

Controlled Clinical Trial ◽

Dentin Hypersensitivity ◽

Molar Incisor Hypomineralisation ◽

Randomised Controlled Clinical Trial ◽

Sensitive Teeth ◽

Randomised Controlled ◽

Incisor Hypomineralisation

IntroductionDentin hypersensitivity (DH) is defined as high sensitivity of the vital dentin when exposed to thermal, chemical or tactile stimuli. Two mechanisms are required for the occurrence of DH: (1) the dentin must be exposed and (2) the dentinal tubules must be open and connected to the pulp. Molar–incisor hypomineralisation (MIH) is a qualitative abnormality of a genetic origin that affects tooth enamel and, in most cases, is accompanied by DH. The control of tooth sensitivity is fundamental to the successful treatment of MIH. The aim of the proposed randomised, controlled, clinical trial is to evaluate the effectiveness of different protocols for the control of DH in patients with teeth affected by MIH.Methods and analysisOne hundred and forty patients who meet the inclusion criteria will be allocated to four groups. Group 1 will be the control group (placebo). In Group 2, sensitive teeth will be sealed with PermaSeal (Ultradent). In Group 3, sensitive teeth will receive low-level laser (LLL, AsGaAl) at a wavelength of 780 nm (Laser XT Therapy, DMC, São Carlos, Brazil). In Group 4, sensitive teeth will be treated with both LLL and PermaSeal (Ultradent). DH will be evaluated 15 min after the application of the treatments and the patients will be reevaluated 1 week, 1 month, 3 months and 6 months after the treatments. The primary outcome of this study is change in pain/sensitivity, when evaluated through a Visual Analogue Scale, to determine the effectiveness of the proposed treatments, as well as differences among the evaluation times for each proposed treatment.Ethics and disseminationThis protocol has been ethically approved by the local medical ethical committee (protocol number: 4.020.261). Results will be submitted to international peer-reviewed journals and presented at international conferences.Trial registration numberNCT04407702.

Download Full-text

The effect of oat bran consumption on gestational diabetes: a randomized controlled clinical trial

BMC Endocrine Disorders ◽

10.1186/s12902-021-00731-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zahra Barati ◽

Mina Iravani ◽

Majid Karandish ◽

Mohammad Hosein Haghighizadeh ◽

Sara Masihi

Keyword(s):

Clinical Trial ◽

Blood Glucose ◽

Gestational Diabetes ◽

Fasting Blood Glucose ◽

Intervention Group ◽

Control Group ◽

Controlled Clinical Trial ◽

Standard Diet ◽

Oat Bran ◽

Significant Difference

Abstract Background Gestational diabetes is the most common medical complication in pregnancy, and it has many side effects for the mother and the fetus. The aim of this study was to evaluate the effect of oat bran consumption on gestational diabetes. Methods This study is a randomized clinical trial that was performed on 112 women with gestational diabetes treated with diet. Participants were randomly divided into two groups of 56. Participants in both groups were given a diet for gestational diabetes. In addition to the diet, the intervention group received 30 g of oat bran daily for 4 weeks at lunch and dinner. Tests of fasting blood glucose and two-hour postprandial (2hpp) glucose were taken from both groups: before the intervention, and 2 and 4 weeks after the start of the intervention. Data analysis was performed using SPSS statistical software (version 22) using independent t-test, as well as Chi-square and Mann-Whitney tests. P values less than 0.05 were considered statistically significant. Results There was no statistically significant difference between the two groups in terms of mean blood glucose before the intervention, while 2 and 4 weeks after the intervention, mean fasting blood glucose and two-hour postprandial (2hpp) glucose decreased significantly in the intervention group compared with the control group (P < 0.001). Conclusion Based on the results of this study, the addition of oat bran to the standard diet for pregnant women with gestational diabetes reduced fasting blood glucose and two-hour postprandial (2hpp) glucose. More detailed studies with higher sample sizes are recommended to prove the effectiveness of this valuable dietary supplement. Trial registration IRCT registration number:IRCT20191220045828N1. Registration date: 2020-04-18. Registered while recruiting.

Download Full-text

Efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia: a protocol for randomised double-blind controlled clinical trial

BMJ Open ◽

10.1136/bmjopen-2020-041958 ◽

2020 ◽

Vol 10 (10) ◽

pp. e041958

Author(s):

Nirmani Yasara ◽

Nethmi Wickramarathne ◽

Chamila Mettananda ◽

Aresha Manamperi ◽

Anuja Premawardhena ◽

...

Keyword(s):

Clinical Trial ◽

Sri Lanka ◽

Intervention Group ◽

Primary Outcome Measure ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Scientific Publications ◽

Double Blind ◽

Fetal Haemoglobin

IntroductionDespite being one of the first diseases to be genetically characterised, β-thalassaemia remains a disorder without a cure in a majority of patients. Most patients with β-thalassaemia receive only supportive treatment and therefore have a poor quality of life and shorter life spans. Hydroxyurea, which has shown to induce fetal haemoglobin synthesis in human erythroid cells, is currently recommended for the treatment of sickle cell disease. However, its clinical usefulness in transfusion-dependent β-thalassaemia is unclear. Here, we present a protocol for a randomised double-blind controlled clinical trial to evaluate the efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia.Methods and analysisThis single-centre randomised double-blind placebo-controlled clinical trial is conducted at the Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Adult and adolescent patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into the intervention or control group. The intervention group receives oral hydroxyurea 10–20 mg/kg daily for 6 months, while the control group receives a placebo which is identical in size, shape and colour to hydroxyurea without its active ingredient. Transfused blood volume, pretransfusion haemoglobin level, fetal haemoglobin percentage and adverse effects of treatment are monitored during treatment and 6 months post-treatment. Cessation or reduction of blood transfusions during the treatment period will be the primary outcome measure. The statistical analysis will be based on intention to treat.Ethics and disseminationEthical approval has been obtained from the Ethics Committee of Faculty of Medicine, University of Kelaniya (P/116/05/2018) and the trial is approved by the National Medicinal Regulatory Authority of Sri Lanka. Results of the trial will be disseminated in scientific publications in reputed journals.Trial registration numberSLCTR/2018/024; Pre-results.

Download Full-text

A randomized controlled clinical trial of the effect of supportive counseling on mental health in Iranian mothers of premature infants

BMC Pregnancy and Childbirth ◽

10.1186/s12884-020-03502-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Leila Seiiedi-Biarag ◽

Mojgan Mirghafourvand ◽

Khalil Esmaeilpour ◽

Shirin Hasanpour

Keyword(s):

Mental Health ◽

Clinical Trial ◽

Premature Infants ◽

Control Group ◽

Controlled Clinical Trial ◽

Randomized Controlled Clinical Trial ◽

Randomized Controlled ◽

Significant Difference ◽

Postpartum Bonding ◽

Supportive Counseling

Abstract Background Premature birth can affect maternal mental health. Considering that the mental health disorder in mothers may play a vital role in the growth and development of their children, therefore, this study was conducted to determine the effect of supportive counseling on mental health (primary outcome), mother-child bonding and infant anthropometric indices (secondary outcomes) in mothers of premature infants. Methods This randomized controlled clinical trial was carried out on 66 mothers with hospitalized neonates in the NICU of Alzahra hospital in Tabriz- Iran. Participants were randomly allocated into two groups of intervention (n = 34) and control (n = 32) through a block randomization method. The intervention group received 6 sessions of supportive counseling (45–60 minutes each session) by the researcher, and the control group received routine care. Questionnaires of Goldberg General Health and the postpartum bonding were completed before the intervention (first 72 hours postpartum) and 8 weeks postpartum. Also, the anthropometric index of newborns were measured at the same time. Results There was no statistically significant difference between the two groups in terms of socio-demographic characteristics. After the intervention, based on ANCOVA with adjusting the baseline score, mean score of mental health (AMD: -9.8; 95% Confident Interval (95% CI): -12.5 to -7.1; P < 0.001) and postpartum bonding (AMD: -10.0; 95% CI: -0.6 to 13.9; P < 0.001) in the counseling group was significantly lower than those of the control group; however, in terms of weight (P = 0.536), height (P = 0.429) and head circumference (P = 0.129), there was no significant difference between the two groups. Conclusions Supportive counseling may improve mental health and postpartum bonding in mothers of premature infants. Thus, it may be recommendable for health care providers to offer it to mothers. Trial registration Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N45. Date of registration: October 29, 2018.

Download Full-text

Outcome of lymph node tuberculosis management with conventional treatment with and without prednisolone

Tropical Doctor ◽

10.1177/0049475520984745 ◽

2021 ◽

pp. 004947552098474

Author(s):

Arjuman Sharmin ◽

Ali Hossain ◽

Nazmul Islam ◽

Zakir H Sarker ◽

Sheikh S Hossain ◽

...

Keyword(s):

Clinical Trial ◽

Lymph Node ◽

Complete Resolution ◽

Conventional Treatment ◽

Symptomatic Improvement ◽

Control Group ◽

Controlled Clinical Trial ◽

Open Label ◽

Lymph Node Tuberculosis ◽

And Control

The outcome of lymph node tuberculosis (LNTB) management with conventional anti-tubercular treatment alone is unsatisfactory. We conducted a randomised open-label controlled clinical trial in the Department of Respiratory Medicine in Government Institute of Dhaka, Bangladesh from April 2017 to March 2019. Compared with controls, 54 patients of LNTB received category 1 anti-tubercular treatment with additional prednisolone after randomisation. Complete resolution in 21/54 (75%) and 7 (26.9%), symptomatic improvement in 26 (92.9%) and 22 (84.6%) and complications in 11 (39.28%) and 16 (61.53%) were observed in the treatment and control group, respectively. Thus, we recommend the use of steroids in this setting.

Download Full-text

Supragingival plaque removal with and without dentifrice: a randomized controlled clinical trial

Brazilian Dental Journal ◽

10.1590/s0103-64402012000300009 ◽

2012 ◽

Vol 23 (3) ◽

pp. 235-240 ◽

Cited By ~ 4

Author(s):

Fabricio B. Zanatta ◽

Raquel P. Antoniazzi ◽

Tatiana M. P. Pinto ◽

Cassiano K. Rösing

Keyword(s):

Clinical Trial ◽

Test Group ◽

Control Group ◽

Controlled Clinical Trial ◽

Separate Analysis ◽

Randomized Controlled Clinical Trial ◽

Significance Level ◽

Plaque Removal ◽

Randomized Controlled ◽

Removal Capacity

The aim of this study was to compare the efficacy of dental plaque removal by brushing with and without conventional dentifrice. Twenty-four students aged 17 to 28 years participated in this randomized controlled clinical trial. Quadrants 1-3 or 2-4 were randomly allocated to the test group (brushing without dentifrice) or control group (brushing with dentifrice). After 72 h of cessation of oral hygiene, Quigley & Hein (Turesky) plaque index was assessed before and after brushing by a calibrated and blind examiner. Overtime and intergroup comparisons were performed by Student's paired sample t-test at 5% significance level. The results showed that both groups after toothbrushing presented statistically significant reductions in plaque, with no differences between them (from 3.06 ± 0.54 to 1.27 ± 0.26 versus from 3.07 ± 0.52 to 1.31 ± 0.23). A separate analysis of the buccal and lingual aspects also showed no significant differences between groups. It may be concluded that the use of a conventional dentifrice during toothbrushing does not seem to enhance plaque removal capacity.

Download Full-text

Curcumin nanomicelle versus curcumin improves lipid profile, stress oxidative factors and inflammatory markers in patients undergoing coronary elective angioplasty; A Randomized Clinical Trial

10.21203/rs.2.18679/v1 ◽

2019 ◽

Author(s):

Bijan Helli ◽

Hadis Gerami ◽

Maria Kavianpour ◽

Habib Heybar ◽

Seyed Kianoosh Hosseini ◽

...

Keyword(s):

Clinical Trial ◽

Lipid Profile ◽

Inflammatory Markers ◽

Interleukin 1 ◽

Stress Index ◽

Inflammatory Factors ◽

Control Group ◽

Controlled Clinical Trial ◽

Double Blind ◽

Stress Oxidative

Abstract Background: Curcumin exhibited antioxidant and anti-inflammatory effects. The aim of this study, assess and compare curcumin and nano- curcumin effects on lipid profile, oxidative stress index and inflammatory factors of heart patients.Methods: This Randomized, Double-Blind, Placebo-Controlled Clinical Trial conducted on 90 patients undergoing coronary elective angioplasty. Patients were randomly divided into 3 groups. The first group received a 500 mg capsule of curcumin daily. The second group received an 80 mg capsule of nano- curcumin daily. The placebo group also received capsules similar to curcumin for 8 weeks. Lipid profile, stress oxidative factors and inflammatory markers measured in baseline and end of the investigation.Results: At the end of study, statistically significant changes was seen in the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) in the intervention groups to the control group (p<0.05). These changes in the nano-curcumin group were greater than the curcumin group. Curcumin and nano-curcumin supplementation also caused a statistically significant improvement in plasma levels of total antioxidant capacity (TAC), malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), high-sensitivity C-reactive protein (hs-CRP), Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in comparison to the placebo (p<0.05).Conclusion: Complementary therapy of cardiovascular patients with curcumin and nano-curcumin supplements, could improve lipid profile, stress oxidative index and, inflammatory factors. The effects of curcumin on nano formula may be better for cardiac patients due to high bioavailability. However, further investigation is suggested in this regard.

Download Full-text

Multidisciplinary Evaluation of Pacifier Removal on Oro-Dentofacial Structures: A Controlled Clinical Trial

Frontiers in Pediatrics ◽

10.3389/fped.2021.703695 ◽

2021 ◽

Vol 9 ◽

Author(s):

Kelly Guedes de Oliveira Scudine ◽

Camila Nobre de Freitas ◽

Kizzy Silva Germano Nascimento de Moraes ◽

Silvana Bommarito ◽

Rosana de Fátima Possobon ◽

...

Keyword(s):

Clinical Trial ◽

Mixed Model ◽

Control Group ◽

Controlled Clinical Trial ◽

Functional Changes ◽

Mixed Model Anova ◽

And Function ◽

Clinical Trials Registry ◽

Facial Anthropometry ◽

Over Time

It is well recognized that pacifier habit leads to occlusal and orofacial functional changes in children. However, the effects of the interruption of prolonged pacifier habit on the development of the dento-facial complex has not yet been fully characterized. Thus, the aim of this study was to investigate the influence of pacifier removal on aspects of oro-dentofacial morphology and function in preschool children. For that, a pacifier group (n = 28) and a control group (n = 32) of 4-year-old children with and without pacifier habit, respectively, were followed up by a group of dentists and speech therapists at baseline, 6 and 12 months after habit removal. Bite force and lip pressure were assessed using digital systems, and the evaluation of breathing and speech functions was performed using validated protocols, together with the measurements of dental casts and facial anthropometry. The Two-way mixed model ANOVA was used in data analysis. After 12 months, a decrease in malocclusion frequency was observed in pacifier group. Additionally, a change over time was observed in facial, intermolar and palate depth measurements, as well in bite and lip forces and speech function scores, increasing in both groups (p < 0.01). The upper and lower intercanine widths and breathing scores differed between groups at baseline and changed over time reducing the differences. The presence of speech distortions was more frequent in the pacifier group at baseline and decreased over time (p < 0.05). The interruption of pacifier habit improved the maxillary and mandibular intercanine widths, as well as the breathing and speech functions, overcoming the oro-dentofacial changes found.Trial Registration: This clinical trial was registered in the Brazilian Clinical Trials Registry (ReBEC; http://www.ensaiosclinicos.gov.br/), protocol no. RBR-728MJ2.

Download Full-text