Clinical Trials in Degenerative Diseases

Role of trace mineral in periodontal health: a review Adiya Apon, Praneeta Kamble Clinical Trials in Degenerative Diseases 2019 4(2):30-36 Periodontal diseases are microbial induced chronic inflammatory conditions characterized by infiltration of leukocytes, loss of connective tissue, alveolar bone resorption, and formation of periodontal pockets. In response to periodontal pathogens, leukocytes elaborate destructive oxidants, proteinases and other factors. Periodontal disease is a chronic inflammatory disease, which leads to alteration of the micronutrient levels such as zinc, selenium, iron and copper. The imbalance of the micronutrient levels leads to increased susceptibility to oxidative damage of tissues. These micronutrients play a role in both health and disease. The vitality of the periodontal tissues in both health and disease depends on the adequate source of essential nutrients being available to the host. Micronutrients are imperative for optimum host response. Populations worldwide are prone to their insufficiency due to lifestyle changes or poor nutritional intake. Balanced levels of these trace minerals such as iron, zinc, selenium and copper are essential to prevent progression of chronic conditions like periodontitis. Their excess as well as deficiency is detrimental to periodontal health. Selenium, zinc and copper are integral components of antioxidant enzymes and prevent reactive oxygen species induced destruction of tissues. Their deficiency can worsen periodontitis associated with systemic conditions like diabetes mellitus. This review focused on the role of micronutrients, namely, iron, zinc, selenium and copper in periodontal health and their association with chronic periodontitis.

Clinical progress of cell therapy in treating age-related macular degeneration Ling Diao, Pan-Feng Fang Clinical Trials in Degenerative Diseases 2019 4(2):37-42 Age-related macular degeneration is a retinal degenerative lesion caused by cell atrophy and dysfunction of retinal pigment epithelium. The degeneration of retinal pigment epithelium cells further leads to the apoptosis of photoreceptor cells, causes vision deterioration and eventually even blindness. Age-related macular degeneration is one of the top three retinal diseases causing blindness in the world. In recent years, exogenous retinal pigment epithelium cell therapy has emerged as a breakthrough treatment for age-related macular degeneration disease. In this review, we will briefly introduce the policies and regulations of cell therapy and discuss the clinical progress in the treatment of age-related macular degeneration using retinal pigment epithelium cells.

Hemodynamic responses of patients with stable coronary artery disease to a comedy film: study protocol for a randomized controlled trial Rosane Maria Nery, Raquel Petry Buhler, Débora Santos Macedo, Juliana Maia Delfino, Filipe Ferrari, Anderson Donelli Silveira, Marco Aurélio Lumertz Saffi, Ricardo Stein Clinical Trials in Degenerative Diseases 2019 4(2):43-48 Background and objective: Alternative and complementary interventions have been developed in an attempt to improve treatment and increase the survival of patients with coronary artery disease (CAD); one such intervention is laughter therapy. However, there is very little information on the effect of this therapeutic modality in patients with CAD. The present randomized controlled trial will compare the effect of 24 sessions of a comedy film and neutral documentary in patients with CAD. Subjects and methods: This is a randomized, parallel-design, examiner-blinded and controlled clinical trial. Patients with stable CAD of both sexes, aged ≥ 18 years, receiving regular follow-up at a public university hospital in Southern Brazil will be included in the trial. Subjects will be randomly allocated to an intervention group (will watch a 30-minute comedy film) or a control group (will watch a 30-minute neutral documentary). Patient recruitment will end in December 2019. Analysis of the primary outcome measure will be completed in December 2019. The current protocol version is 1.0. The study protocol was approved by the Institutional Review Board of Hospital de Clínicas de Porto Alegre (protocol No. 13-0124) on July 9, 2013. Outcome measures: The primary outcomes are the difference from baseline to the 2-month time point (corresponding to 24 sessions) in endothelial function, as assessed by brachial artery flow-mediated dilation measurement and peak oxygen consumption (peak VO2) on cardiopulmonary exercise testing. Secondary outcome measures include concentrations of inflammatory markers in blood, biochemical parameters, and quality of life. Discussion: This study will provide new evidence on the effect of an easy-to-use, inexpensive, readily deployable non pharmacological therapeutic intervention for patients with stable CAD. Trial registration: ClinicalTrials.gov identifier: NCT02824120. Date of registration: July 6, 2016.

Tanreqing injection with ambroxol hydrochloride for heart failure and pulmonary infection in senile degenerative heart disease: a randomized controlled trial Guang-Qiang Zhao Clinical Trials in Degenerative Diseases 2019 4(2):49-55 Background and objective: Degenerative changes in the heart with age and decreased immune function mean that older adult patients with heart failure are vulnerable to infection by pathogenic bacteria. Tanreqing injection, a traditional Chinese compound medicine, has the functions of clearing heat, eliminating phlegm, and detoxifying, and can be used to treat pulmonary infection. We hypothesized that Tanreqing injection combined with ambroxol hydrochloride, a mucolytic drug, may effectively alleviate pulmonary infection and improve cardiac function in older adult patients with heart failure and pulmonary infection caused by degenerative heart disease. Participants and methods: This prospective, single-center, randomized, controlled clinical trial will include 320 patients with heart failure combined with pulmonary infection induced by senile degenerative heart disease from Sanya People’s Hospital, Sanya, China. All patients will receive conventional anti-heart failure treatment, and will be equally and randomly divided into a control group and a trial group. Patients in both groups will be treated with intravenous infusion of ambroxol hydrochloride, while patients in the trial group will additional receive Tanreqing injection. The treatment period will be 7 days. Patient recruitment and data collection will begin on July 1, 2019 and end on August 30, 2021. Analysis of the results will be performed from September 10–30, 2021. This study is scheduled to end on December 30, 2021. The study protocol was approved by the Medical Ethics Committee of Sanya People’s Hospital in October 2015 (approval No. S2015-065-03). Study protocol version is 1.0. This study will be performed in accordance with the principles of the Declaration of Helsinki. Written informed consent to participate will be obtained from participants or their family members. Results: The primary outcome measure is total effective rate after 7 days of treatment. Secondary outcome measures are change from baseline in left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, left ventricular fractional shortening, number of pathogenic bacteria in the lung, serum procalcitonin level, and C-reactive protein level after 7 days of treatment, as well as incidence of adverse reactions after 7 days of treatment. In a pilot study among 120 patients with senile heart failure conducted from May 2016 to October 2017, patients were randomly assigned to trial and control groups (n = 60 per group). Gram-positive bacteria were found to be the main pathogens responsible for pulmonary infection in senile patients with heart failure, with a positive rate of 53.7% in both control and trial groups. After treatment, the number of pathogenic bacteria in the trial group was markedly lower than that in the control group (11 strains versus 17 strains). Furthermore, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular ejection fraction were significantly lower (P < 0.05) after treatment, but left ventricular fractional shortening was significantly higher (P < 0.05). Serum procalcitonin and C-reactive protein levels were significantly decreased (P < 0.05) in both groups after treatment, although the changes were more significant in the trial group compared with the control group (P < 0.05). Conclusion: The results of this planned study will confirm whether Tanreqing injection combined with ambroxol hydrochloride can markedly improve cardiac function in senile patients with heart failure and mitigate pulmonary infection caused by pathogenic bacteria. This study will also identify adverse drug reactions associated with the study treatment. Trial registration: This study was registered with the Chinese Clinical Trial Registry on April 29, 2019 (registration number: ChiCTR1900022879).

Relationship between low vitamin D status and extra-skeletal diseases: a systematic review on effects of prophylaxis with vitamin D Lorella Magnani Clinical Trials in Degenerative Diseases 2019 4(2):56-63 Background and objective: A recent body of observational evidence has suggested that the low vitamin D status is related to various diseases, both skeletal and extra-skeletal muscle, including cardiovascular disease, chronic obstructive pulmonary disease and cystic fibrosis, inflammatory bowel disease, cancer, diabetes, immune system diseases (allergies), generating a growing use of supplementation, and at high doses. We conducted this systematic review with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)statement, to summarize the scientific literature concerning the role of low-level vitamin D in the extra-skeletal outcomes and the effects of supplementation. Materials and methods: Articles from PubMed, MEDLINE,and Cochrane Library were searched. Finally, 18 systematic reviews/meta-analyses, 11 documents of scientific societies/guidelines/editorials/books, and 19 interventions and observational studies (of which 5 randomized controlled trials) were included. Results: It has been found that, despite there is a large amount of observational cohort studies and anecdotal evidence of the benefits of vitamin D supplementation both on skeletal and extra-skeletal outcomes, more research is needed to verify the causality (and not only correlation) of low vitamin D status on extra-skeletal outcomes, considering that solid evidence from randomized controlled trials or other intervention studies are few, that the results of different randomized controlled trials cancel each other coming to opposite conclusions and that pervasive methodological defects make the evidence unreliable. Conclusion: Vitamin D supplementation for extra-skeletal outcomes does not seem justified, if not in clinically documented deficiencies or in specially designed clinical trials.

CTDD call for papers Clinical Trials in Degenerative Diseases 2019 4(2):64-64