scholarly journals Daily Oral Administration of the Novel Androgen 11β-MNTDC Markedly Suppresses Serum Gonadotropins in Healthy Men

2020 ◽  
Vol 105 (3) ◽  
pp. e835-e847 ◽  
Author(s):  
Fiona Yuen ◽  
Arthi Thirumalai ◽  
Cindy Pham ◽  
Ronald S Swerdloff ◽  
Bradley D Anawalt ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Double Blind Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Healthy Men ◽  
Drug Concentrations ◽  
Serum Gonadotropin

Abstract Background 11β-methyl-19-nortestosterone (11β-MNT) is a modified testosterone (T) with androgenic and progestational activity. A single oral dose of the prodrug, 11β-MNT dodecylcarbonate (11β-MNTDC), was well tolerated in healthy men. Methods We conducted a randomized, double-blind study at 2 academic medical centers. 42 healthy men (18–50 years) were randomized to receive oral placebo or 11β-MNTDC, 200 or 400 mg daily, for 28 consecutive days. Primary outcome (safety and tolerability) measures were assessed twice per week. Subjects underwent serial blood sampling over 24 hours on days 1 and 28 to assess secondary outcomes: pharmacokinetics (serum drug concentrations); pharmacodynamics of 11β-MNTDC (serum sex steroids and gonadotropins); and mood and sexual function (via validated questionnaires). Results There were no serious adverse events. No participants discontinued because of an adverse event or laboratory test abnormality. 11β-MNTDC resulted in a dose-related increase in serum 11β-MNTDC and 11β-MNT concentrations sustained over 24 hours. Administration of 11β-MNTDC resulted in a marked suppression of serum gonadotropins, T, calculated free T, estradiol, and SHBG over the treatment period (P < 0.01). Adverse effects that may be related to 11β-MNTDC included weight gain, acne, headaches, fatigue, and mild mood changes, with 5 men reporting decreased libido and 3 decreased erectile/ejaculatory function. Serum low-density lipoprotein cholesterol, weight (~2 kg), hematocrit, and hemoglobin increased and serum high-density lipoprotein cholesterol decreased in both 11β-MNTDC groups. Conclusion Daily oral 11β-MNTDC for 28 days in healthy men markedly suppressed serum gonadotropin and T concentrations without serious adverse effects. These results warrant further evaluation of 11β-MNTDC as a potential male oral contraceptive.

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

scholarly journals Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia

2005 ◽  
Vol 153 (5) ◽  
pp. 679-686 ◽  
Author(s):  
Cheng-Chieh Lin ◽  
Tsai-Chung Li ◽  
Ming-May Lai
Keyword(s):  
Total Cholesterol ◽  
Apolipoprotein B ◽  
Clinical Laboratory ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Monascus Purpureus ◽  
Lipid Lowering ◽  
Controlled Study ◽  
Double Blind

Objective: The purpose of this study was to assess the lipid-lowering effect of Monascus purpureus Went rice on serum lipids in patients with hyperlipidemia, and to assess its safety by reporting adverse events and clinical laboratory measurements. Design and methods: This was a randomized, double-blind, placebo-controlled study. In all, 79 patients (aged 23–65 years) with a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 5.28 mmol/l (203.9 mg/dl) received a twice daily dose of placebo or Monascus purpureus Went rice (600 mg) for 8 weeks. Results: At week 8, Monascus purpureus Went rice therapy reduced LDL-C by 27.7%, total cholesterol by 21.5%, triglycerides by 15.8% and apolipoprotein B by 26.0%. High-density lipoprotein cholesterol and apolipoprotein A-I levels were increased by 0.9 and 3.4% respectively (not significant). No patient in the Monascus purpureus Went rice treatment group had an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatine phosphokinase (CPK) measurement that was ≥ 3 times the upper limit of normal at week 4 and week 8. Conclusion: Monascus purpureus Went rice significantly reduced LDL-C, total cholesterol, triglycerides and apolipoprotein B levels, and was well tolerated in patients with hyperlipidemia. However, this study only provides data from an 8-week trial and long-term safety and efficacy data are needed.

scholarly journals Metabolic and Clinical responses to Bunium Persicum (Black Caraway) supplementation in overweight and obese patients with type 2 diabetes: a double-blind randomized placebo-controlled clinical trial

2020 ◽  
Author(s):  
Saber Jafari-Maskouni ◽  
Mansour Shahraki ◽  
Milad Daneshi-Maskooni ◽  
Alireza Dashipour ◽  
Ali Shamsi-Goushki ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Glucose ◽  
Lipoprotein Cholesterol ◽  
Controlled Clinical Trial ◽  
Model Assessment ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Bunium Persicum ◽  
Clinical Responses

Abstract Background: Diabetes mellitus is the most common metabolic disorder worldwide. We aimed to determine the effects of Bunium Persicum (BP) on serum glucose indices, lipid profile, and nesfatin-1 levels in overweight or obese T2DM patients.Methods: Participant recruitment took place in the diabetic clinic of Bu-Ali hospital in Zahedan. Based on the eligibility criteria, 60 participants were randomly divided into two groups, namely BP (n=30) and placebo (n=30). The supplementation was one 1000 mg capsule 2 times /day BP with meals (lunch and dinner) for 8 weeks. Bodyweight, waist circumference, serum nesfatin-1, fasting blood sugar (FBS) and insulin (FBI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. Quantitative insulin sensitivity checks index (QUICKI), homeostasis model assessment-insulin resistance (HOMA-IR), and Body Mass Index (BMI) were also calculated.Results: In comparison with placebo, BP significantly decreased FBS, HOMA-IR, and BMI (P<0.05). The differences in the FBI, QUICKI, TG, TC, LDL, HDL, WC, and Nesfatin-1 were not significant (P>0.05).Conclusion: BP supplement improved serum glucose indices and decreased BMI among overweight or obese T2DM patients; though, further trials are suggested to confirm results.Trial Registration: Iranian Registry of Clinical Trials (IRCT), IRCT20181207041876N1, Registered 18/01/2019, https://irct.ir/trial/35752

Niacin Treatment of Hypercholesterolemia in Children

PEDIATRICS ◽  
1993 ◽  
Vol 92 (1) ◽  
pp. 78-82
Author(s):  
Richard B. Colletti ◽  
Nancy K. Roff ◽  
Ellis J. Neufeld ◽  
Annette L. Baker ◽  
Jane W. Newburger ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Total Serum ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Serum Aminotransferase ◽  
Hospital Referral

Objective. To determine the efficacy and adverse effects of niacin treatment of hypercholesterolemia in children. Design. Retrospective review. Setting. Two university hospital referral clinics. Patients. All children who received single-drug niacin treatment for severe hypercholesterolemia between 1980 and 1991. Results. Twenty-one children, aged 4 to 14 years, were treated with niacin, 500 to 2250 mg daily. Pretreatment total serum cholesterol value (mean ± SD) was 7.84 ± 1.14 mmol/L (303 ± 44 mg/dL), and low-density lipoprotein cholesterol value was 6.28 ± 1.16 mmol/L (243 ± 45 mg/dL). Niacin treatment in daily doses &gt;1000 mg reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30% (P &lt; .001) but had no effect on highdensity lipoprotein cholesterol and triglycerides. As in adults, reversible adverse effects were common, occurring in 16 (76%) of the 21 children. Six children (29%) had reversible dose-related elevations of serum aminotransferase levels. Niacin therapy was discontinued in 8 children (38%) because of flushing, abdominal pain, vomiting, headache, or elevated serum aminotransferase levels. Conclusions. This study suggests that although niacin treatment in children is efficacious, adverse effects are common. Until further study demonstrates long-term safety, niacin treatment should be reserved for the closely-supervised treatment of severe hypercholesterolemia by a lipid specialist.

scholarly journals Supplementation with Low Doses of a Cod Protein Hydrolysate on Glucose Regulation and Lipid Metabolism in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1991 ◽  
Author(s):  
Caroline Jensen ◽  
Hanna Fjeldheim Dale ◽  
Trygve Hausken ◽  
Jan Gunnar Hatlebakk ◽  
Ingeborg Brønstad ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Composition ◽  
Lipid Profile ◽  
Protein Hydrolysate ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Postprandial Glucose ◽  
Double Blind Study ◽  
Double Blind ◽  
Glucose Levels

The risk of cardiovascular diseases and type 2 diabetes mellitus are increased in subjects with metabolic syndrome (MetS), and hydrolyzed fish protein may have favorable effects on metabolic health. Here, we investigated the effect of 8 weeks supplementation with 4 g of cod protein hydrolysate (CPH) on glucose metabolism, lipid profile and body composition in individuals with MetS in a double-blind, randomized intervention study with a parallel-group design. Subjects received a daily supplement of CPH (n = 15) or placebo (n = 15). Primary outcomes were serum fasting and postprandial glucose levels. Secondary outcomes were fasting and postprandial insulin and glucagon-like peptide 1 (GLP-1), fasting lipid concentrations and body composition. No difference was observed between CPH and placebo for insulin, glucose or GLP-1 after 8 weeks intervention. Fasting triacylglycerol decreased in both the CPH group and placebo group, with no change between groups. Fasting total cholesterol and low-density lipoprotein cholesterol decreased significantly within both groups from baseline to study end, but no difference was observed between the two groups. In conclusion, supplementing with a low dose of CPH in subjects with MetS for 8 weeks had no effect on fasting or postprandial levels of insulin, glucose or GLP-1, lipid profile or body composition.

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