Randomized response surface pathway design with skewed starting point and stochastic dose window
DOI:
https://doi.org/10.18203/2349-3259.ijct20200202Keywords:
Response surface pathway design, Skewed starting value, Stochastic dose-window, IL-1β mRNA expression, BP-C2, SalmonAbstract
Background: The aim was to introduce response surface pathway (RSP)-design with skewed starting value and stochastic dose-window to estimate optimal efficacy dose (OED) of BP-C2 after IL-1β stimulation in Atlantic salmon.
Methods: 54 healthy smolt of Atlantic salmon between 50 and 100 g before habituated to salt water were included. The study was conducted as a one-dimensional, randomized between-patient three-level RSP designed trial with one interventional- and one response variable and odd outcomes. The interventional variable was intraperitoneal injected BPC2 with skewed starting dose of 0.10 mg/100 g related to the initial dose-window <0.02-0.5 mg/100 g. The response variable was the Ct-value of mRNA IL-1β expression 24 hours after injection.
Results: Skewed starting value of 0.10 mg/100 g was chosen in the first design-level with a dose-window of <0.0-0.20]. The three smolt obtained a reduction in Ct-value above 15%, and the dose-window adjusted with the lower boundary equals the previous dose. The five smolt at second design-level received 0.16 mg/100g with a dose-window [0.10-0.22]. Four smolt obtained above 15% and one of 0.5% reduction in cycle threshold (Ct)-value. Six smolt in the third design-level received 0.21 mg/100 g and one 0.16 mg/100 g. The mean Ct-value was reduced from 30.0 in the unstimulated situation to 25.0, 24.8 and 26.4 after BP-C2 stimulation of 0.10, 0.16 and 0.21 mg/100 g, respectively. The OED of BP-C2 related to IL-1β was estimated to 0.14 mg/100 g.
Conclusions: Skewed starting value in the initial dose-window made the K-adjustment factor and dose-window stochastic. The RSP-procedure works in accordance to the expectation and estimated OED of BP-C2 sufficiently.
References
Hastein T, Gudding R, Evensen O: Bacterial vaccines for fish- an update of the current situation worldwide. Develop Biol. 2005;121:55-74.
Gudding R, Lillehaug A, Evensen O: Recent developments in fish vaccinology. Veter Immunol Immunopathol. 1999;72(1-2):203-12.
Evensen O, Brudeseth B, Mutoloki S: The vaccine formulation and its role in inflammatory processes in fish--effects and adverse effects. Develop Biol. 2005;121:117-25.
Jorgensen JB, Johansen A, Stenersen B, Sommer AI. CpG oligodeoxynucleotides and plasmid DNA stimulate Atlantic salmon (Salmo salar L.) leucocytes to produce supernatants with antiviral activity. Develop Compar Immunol. 2001;25(4):313-21.
Jorgensen JB, Johansen LH, Steiro K, Johansen A. CpG DNA induces protective antiviral immune responses in Atlantic salmon (Salmo salar L.). J Virol. 2003;77(21):11471-9.
Jorgensen JB, Zou J, Johansen A, Secombes CJ. Immunostimulatory CpG oligodeoxynucleotides stimulate expression of IL-1beta and interferon-like cytokines in rainbow trout macrophages via a chloroquine-sensitive mechanism. Fish Shellfish Immunol. 2001;11(8):673-82.
Fedoros EI, Orlov AA, Zherebker A, Gubareva EA, Maydin MA, Konstantinov AI, et al. Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro. Oncotarget. 2018;9(26):18578-93.
Dewi S, Larsen S, Sirmuninnimit V, u Y-S, Lindkaer-Jensen S, Manuaba TW. Benzene-poly-carboxylic acids complex with cis-diammineplatinium (II) dichloride in treatment of stage IV breast cancer patients. Open Breast Cancer J. 2013;5:7-15.
Larsen S, Butthongkomvong K, Manikhas A, Trishkina E, Poddubuskaya E, Matrosova M, et al. BP-C1 in treatment of patients with sage IV breast cancer: a randomized, double-blind, placebo-controlled multicentre study and an additional open-label treatment phase. Breast Cancer: Target Therap. 2014;6:179-89.
Butthongkomvong K, Raunroadroong N, Sorrarichingchai S, Sangsaikae I, Srimuninnimit V, Harling H, et al. Efficacy and tolerability of BP-C1 in metastatic breast cancer: a Phase II, randomized, double-blind, and placebo-controlled Thai multi-center study. Breast Cancer- Target Therap. 2019;11:1143-51.
Lindkær-Jensen S, Larsen S, Lindkaer-Jensen NH, Fagertun HE. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV of BP-C1: a new anticancer substance. Drug Design Develop Therap. 2015;9:1881-90.
Kristiansen VM, Dewi S, Horsberg TE, Jonasdottir TJ, Moe L, Berlinger B, et al. Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary tumours. Veter Compar Oncol. 2015;13:118-32.
Dewi S, Kristiansen V, Lindkær-Jensen S, Larsen S. Between- and within-patient n-level response surface pathway design to reduce animal numbers in toxicity studies. Open Access J Clin Trial. 2014;6:63-74.
Ibrahim T, Larsen S, Lindkær-Jensen NH, Lindkær-Jensen S. BP-C2 improve Functional status, Quality of Life and Corrects Biochemical Imbalances as Adjuvant Therapy to FOLFIRINOX Treatment: A Case of Advanced Inoperable Pancreatic Cancer. J Clin Case Rep. 2015;5:514-17.
Fares F, Azzam N, Fares B, Larsen S, Lindkær-Jensen S. Benzene-poly-carboxylic acid complex, a novel anti-cancer agent induces apoptosis in human breast cancer cells. Plos One 2014;9:e851-6.
Immunological study of BP-C2, BP-CX-1 and BP-C1. Institute of Cancer Biology, Danish Cancer Society; Research Report 2011 (Manuscript for publication in process).
Fabian NJ, Albright LB, Gerlach G, Fisher HS and Rosenthal GG. Humic Acid Interferes with Species Recognition in Zebrafish (Danio rerio). J Chem Ecol. 2007;33:2090-6.
Abdel-Wahab AM, El-Refaee AME, Ammar AA. Effects of humic acid as feed additive in improvement of nonspecific immune response and disease resistance in common Carp (Cyprinus carpio). Egypt J Aquaculture. 2012;2:83-91.
Dewi S, Aune T, Buanæs JAA, Smith AJ, Larsen S. The development of response surface pathway design to reduce animal numbers in toxicity studies. BMC Pharmacol Toxicol. 2014;15-8.
Chick H. An investigation of the laws of disinfection. J Hygiene. 2013;8(1):92-158.
Holand T, Ellingsen K, Dewi S, Larsen. Randomized response surface pathway design with odd response outcomes in a Latin Square designed study. Open Access J Clin Trial. 2017;9:75-84.
Fisher G: Series and Sequences. Phoenix Education: Putney; 1996.
Altman DG. Practical Statistic for Medical Research. London: Chapman and Hall; 1991.
Paul RK, Rosenberger WF, Flournoy N. Quantile estimation following non-parametric phase I clinical trials with ordinal response. Stat Med. 2004;23(16):2483-95.
Kleinbaum DG, Kupper LL, Muller KE, Nizam A. Applied Regression Analysis and Other Multivariable Methods. 3rd ed. Pacific Grove: Duxbury Press; 1998.
Hennessey VG, Rosner GL, Bast RC, Chen MY. A Bayesian approach to dose-response assessment and synergy and its application to in vitro dose-response studies. Biometrics. 2010;66(4):1275-83.
Grieve AP, Krams M. ASTIN: a Bayesian adaptive dose- response trial in acute stroke. Clin Trial. 2005;2:340-51.
Tan H, Gupta P, Harness J, Wolk R, Chapel S, Menter A, et al. Dose response and pharmacokinetics of tofacitinib (CP-690,550), an Oral Janus kinase inhibitor, in the treatment of chronic plaque psoriasis. CPT Pharmacometrics Syst Pharmacol. 2013;2(5):44.
Holand T, Dewi S, Larsen S. Development of a randomized two-dimensional response surface pathway design with two interventional and one response variables. Open Access J Clin Trial. 2016;8:33-42.
Larsen S, Holand T, Bjørnæs K, Glomsrød E, Kaufmann J, Garberg TH, et al. Randomized two dimensional between patient response surface pathway design with two interventional and one response variable in estimating minimum efficacy dose. Intl J Clin Trial. 2019;6(3):75-83.
Wangkahart E, Secombes CJ, Wang T. Studies on the use of flagellin as an immunostimulant and vaccine adjuvant in fish aquaculture. Frontier Immunol. 2019;9:1-22.
