scholarly journals BuqiTongluo Granule for Ischemic Stroke, Stable Angina Pectoris, Diabetic Peripheral Neuropathy with Qi Deficiency and Blood Stasis Syndrome: Rationale and Novel Basket Design

2021 ◽  
Vol 12 ◽  
Author(s):  
Weidi Liu ◽  
Li Zhou ◽  
Luda Feng ◽  
Dandan Zhang ◽  
Chi Zhang ◽  
...  

Background: BuqiTongluo (BQTL) granules are herbal phenotypic drugs for Qi deficiency and blood stasis (QDBS) syndrome. Its discovery relied primarily on knowledge of observable phenotypic changes associated with diseases. Although BQTL granules have been widely advocated by Chinese Medicine (CM) practitioners, its use lacks empirical support.Aim of the study: In this basket trial, the efficacy of BQTL granules in multiple diseases that have the QDBS syndrome in common will be compared with placebo.Materials and Methods: The BuqiTongluo granule for Qi deficiency and blood stasis syndrome (BOSS) study is a basket herbal trial (ClinicalTrials.gov, NCT04408261). It will be a double-blinded, randomized, placebo-controlled, parallel, multicenter, clinical trial. In total, 432 patients (1:1:1 ischemic stroke, stable angina pectoris, and diabetic peripheral neuropathy), who meet the operationalized diagnostic criteria for QDBS syndrome, have been recruited and randomized in a ratio of 1:1 to receive 6 weeks’ treatment with BQTL granules or placebo. The primary outcome is the change in the QDBS syndrome score at week 6 from baseline. Secondary outcomes include objective outcome measures for the three diseases and adverse events. Omics will help to understand these responses by molecular events.Conclusion: QDBS syndrome is a common phenotypic marker that was hypothesized to predict whether patients with multiple diseases would respond to this targeted therapy. No previous basket trial has assessed the potential efficacy of an herbal intervention for multiple diseases. The unique promise of the trial is its ability to exploit a disease phenotype to discover novel treatments for three diseases for which the root cause is unknown, complex, or multifactorial, and for which scientific understanding is insufficient to provide valid molecular targets.

1996 ◽  
Vol 76 (02) ◽  
pp. 166-170 ◽  
Author(s):  
Moniek P M de Maat ◽  
Alf E R Arnold ◽  
Stef van Buuren ◽  
J H Paul Wilson ◽  
Cornells Kluft

SummaryElevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz. the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen β-gene.The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the BclI polymorphism of the fibrinogen β-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immuno assay (EIA).In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student t-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen β-gene polymorphisms.Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen β-gene polymorphisms.


2008 ◽  
Vol 149 (7) ◽  
pp. 291
Author(s):  
Viktor Nagy ◽  
István Czuriga

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
MM Svenningsson ◽  
I Dhar ◽  
GFT Svingen ◽  
EKR Pedersen ◽  
D Nilsen ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background/Aim Increased plasma trimetyllysine (TML), a methylated amino acid, has recently been linked to higher risk of acute myocardial infarction (AMI). TML is also a precursor of trimethylamine-N oxide (TMAO), which has been linked to increased cardiovascular risk, including that of  atrial fibrillation (AF). We investigated the association between TML and new-onset AF in two large Norwegian cohorts. Methods The primary cohort consisted of 6396 participants in the community-based Hordaland Health Study (HUSK). The validation cohort consited of 2027 patients who underwent coronary angiography due to suspected stable angina pectoris in the Western Norway Coronary Angiography Cohort (WECAC). Information on new-onset AF was obtained by linking patient data to Norwegian public health registries. Risk associations were explored by Cox regression. Results During median (25th-75th percentile) follow-up of 10.9 (10.6-11.3) and 7.0 (6.3-8.6) years, 560 (8.8%) patients in the HUSK and 210 (10.4%) in the WECAC was diagnosed with AF. In the HUSK, the age and gender adjusted HR (95 % CI) for the 4th vs. 1st plasma TML quartiles 1.84 (1.37-2.48) p &lt; 0.001. In multivariable models the association was only slightly attenuated. Correspondingsly, the age and gender adjusted HR (95% CI) for the 4th vs. 1st TML quartiles in the WECAC was 1.48 (0.96-2.27) p = 0.07. Testing for collinearity between TMAO and TML revealed variance inflation factors between 1.0-1.1 in HUSK and WECAC, thus ruling out collinearity. Conclusion Plasma TML was associated with new-onset AF among subjects from the general population, and the relationship was independent from established AF risk factors. A similar trend was also seen in patients with suspected stable angina pectoris, strengthening our findings, which motivate further studies to explore potential pathophysiological relationships between one-carbon metabolism and cardiac arrhythmias


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Koga ◽  
S Ikeda ◽  
R Akashi ◽  
Y Yamagata ◽  
T Yonekura ◽  
...  

Abstract Background Klotho, which was originally identified as an aging suppressor, is a key regulator of bone and mineral metabolism. Transmembrane and soluble forms of Klotho protein have been identified. The transmembrane form serves as an obligate co-receptor for fibroblast growth factor 23 (FGF23). However, the physiological importance of soluble form of Klotho has not been determined. Purpose The present study aimed to test the hypothesis that circulating soluble Klotho levels can predict the presence or extent of coronary artery calcification (CAC) in patients with coronary artery disease. Methods We analyzed CAC of culprit lesions in patients with 75 stable angina pectoris who were not on dialysis and were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). Arc and length of each calcium within the culprit lesion was measured by IVUS. The main outcome measure was the calcium index; a volumetric IVUS-derived measure which was calculated as total calcium length/lesion length × maximal calcium arc/360°. Low calcium index was defined as calcium index <0.042 of the first quartile value. Serum Klotho and FGF23 were measured before PCI. Patients were divided into two groups according to median serum Klotho value: low-Klotho (n=37, ≤460 pg/mL) and high-Klotho group (n=38, >460 pg/mL). Results Compared with patients with low-Klotho, those with high-Klotho had higher estimated glomerular filtration rate (eGFR) (69±20 vs. 55±16 mL/min/1.73 m2, p<0.001), lower FGF23 levels (51±24 vs. 67±41 pg/mL, p=0.010). Patients with high-Klotho had significantly lower calcium index than those with low-Klotho (0.17±0.21 vs. 0.24±0.23, p=0.043). Serum Klotho levels correlated significantly and inversely with calcium index (r=−0.31, p=0.006). The correlation between Klotho and calcium index was pronounced at analysis in patients with eGFR <60 mL/min/1.73 m2 (r=−0.52, p<0.001). Logistic regression analysis showed that high-Klotho is a sole significant independent factor associated with low calcium index (odds ratio 7.17, p=0.004). Presence of high-Klotho had high sensitivity and negative predictive value for identifying low calcium index (83% and 92%, respectively). Conclusions Serum Klotho values were independently and inversely associated with the degree of CAC assessed by IVUS. These findings have important clinical implications for serum Klotho as a biomarker that reflects the extent of CAC.


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