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Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol.

ABSTRACT: INTRODUCTION:Dehydroepiandrosterone (DHEA) has been proposed to improve pregnancy rates in women with diminished ovarian reserve undergoing in vitro fertilisation (IVF) treatment. However, evidence regarding its efficacy is supported by a limited number of randomised controlled trials (RCTs). This double-blinded RCT aims to measure the effect of DHEA supplementation prior to and during controlled ovarian hyperstimulation on ovarian response prior to IVF treatment in women predicted to have poor ovarian reserve. METHODS AND ANALYSIS:Sixty women with ovarian antral follicle count ?10 and serum anti-Mullerian hormone ?5 pmol/L undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment at the Nurture fertility clinic, Nottingham will be recruited. They will be randomised to either receive DHEA capsule 75?mg/day or placebo for at least 12?weeks before egg collection. All participants will undergo standard long down regulation protocol using human menopausal gonadotropin 300?IU/day. Serum samples and follicular fluids at the time of egg collection will be collected for hormonal immunoassays. For ICSI participants, cumulus cells stripped from oocyte will be collected for cumulus gene expression analyses regarding oocyte competence. Microdrops of oocyte culture media before the time of ICSI will be assessed for glucose, pyruvate and lactate utilisation. Embryo transfer will be performed on day 2, 3 or 5 based on the number and quality of the embryos available. Pregnancy will be defined as urine pregnancy test positive (biochemical pregnancy) and 6-8?weeks ultrasound scan with fetal heart beat (clinical pregnancy) and live birth. It is planned to perform the molecular and nutritional fingerprint analyses in batches after finishing the clinical phase of the study. ETHICS AND DISSEMINATION:The approval of the study was granted by the NHS Research Ethics Committee (Ref number NRES 12/EM/0002), the Medicines and Healthcare products Regulatory Agency (MHRA), and the Nottingham University Hospitals Trust Research and Development department. All participants shall provide written informed consent before being randomised into allocated treatment groups. TRIAL REGISTRATION NUMBER:Protocol V.2.0; EudraCT number: 2011-002425-21; http://www.clinicaltrials.gov; NCT01572025; CTA reference: 03057/0053/001-0002.

SUBMITTER: Jayaprakasan K

PROVIDER: S-EPMC4194749 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol.

Jayaprakasan Kannamannadiar K Narkwichean Amarin A Maalouf Walid E WE Campbell Bruce K BK

BMJ open 20141008 10

<h4>Introduction</h4>Dehydroepiandrosterone (DHEA) has been proposed to improve pregnancy rates in women with diminished ovarian reserve undergoing in vitro fertilisation (IVF) treatment. However, evidence regarding its efficacy is supported by a limited number of randomised controlled trials (RCTs). This double-blinded RCT aims to measure the effect of DHEA supplementation prior to and during controlled ovarian hyperstimulation on ovarian response prior to IVF treatment in women predicted to ha ...[more]

PMID: 25296654

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Project description:IntroductionTungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment.Methods and analysisThis trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6-15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction.Ethics and disseminationThe trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal.Trial registration numbersAustralian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

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Project description:IntroductionAngiosarcoma is a rare and aggressive malignancy with a high metastatic potential and recurrence rate. Despite optimal treatment with surgery, with or without radiation, the prognosis remains poor and, therefore, new treatment strategies are warranted. Recently, propranolol has effectively been repurposed for the treatment of infantile haemangioma. Propranolol is a β3-sparing antagonist of the β-adrenergic receptor. In infantile haemangioma, the β1, β2 and β3 receptors are highly expressed. Angiosarcoma has several similarities with haemangioma, including its high β-adrenergic receptor expression and the supposedly important role of vascular endothelial growth factor in malignant growth. As a result, propranolol has been administered small scale in individual angiosarcoma cases with promising results. The precise effect of propranolol, however, is not yet established.Methods and analysisThe goal of this neoadjuvant window of opportunity study is to prospectively evaluate the activity of propranolol monotherapy in patients with cutaneous angiosarcoma. The neoadjuvant setting provides a good opportunity to rapidly evaluate both the clinical response and histological response, without a significant delay in standard anticancer treatment. Fourteen patients with primary, recurrent or metastatic cutaneous angiosarcoma will be included. Propranolol will be administered orally in an escalating dose during 3-6 weeks, before the initiation of standard treatment. The primary endpoint is clinical response according to Response Evaluation Criteria in Solid Tumours, as measured on consecutive coloured photographs or CT/MRI. The histological response will be determined as secondary endpoint, comparing the difference in proliferation index before and after propranolol by measuring the change in immunohistochemistry staining of Ki-67. The study will be considered positive when at least three patients have a response to propranolol.Ethics and disseminationEthical approval was obtained from the Medical Ethical Committee of the Netherlands Cancer Institute. Independent of the outcome, results of this study will be shared and submitted for publication in an international peer-reviewed journal.Trial registration numberNL8118; registry through the Netherlands Trial Register.

Project description:IntroductionThe skin undergoes morphological and physiological changes with the advancing age of an individual. These changes may be caused by intrinsic and extrinsic factors that contribute to cellular ageing and consequent skin ageing. The term photoageing is used to characterise the ageing of the skin caused by solar radiation. Clinically, the skin becomes more flaccid, thicker and hyperpigmented, while there is an early appearance of wrinkles and other skin changes, such as skin cancer. Nowadays, there are numerous treatments for ageing skin, and one of them is with the use of phototherapy, which uses light-emitting diodes (LEDs). The objective of this study will be to evaluate the percentages of reduction in the volume of periocular wrinkles when treated with red and amber LEDs.Methods and analysisAll of the participants will receive photobiomodulation to treat their periocular wrinkles. They will be using red and amber LEDs, with one colour being used on each hemiface. The facial side to be treated with each colour will be randomised. After an interval of 180 days, the participants will receive a cross-treatment. The primary variable of the study is the volume of periocular wrinkles (crow's feet), which will be measured by a VisioFace equipment. The secondary variables are elasticity (measured by Cutometer) and hydration (measured by Corneometer). Quality of life and self-assessment of the participants will be measured using the adapted Melasma Quality of Life scale - Brazilian Portuguese adaption (MelasQoL-BP) and Skindex-29 questionnaires. All of the variables will be measured before and after a group of 10 sessions.Ethics and disseminationThis protocol was approved by the Research Ethics Committee of the Nove de Julho University (acceptance number: 2.550.732). This trial has been registered in the Registro Brasileiro de Ensaios Clínicos (Brazilian Clinical Trials Registry) (REBEC number: RBR-6YFCBM). This study is not recruiting yet.Trial registration numberRBR6YFCBM; Pre-results.

Dataset Information

Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol.

Publications

Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol.

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