Clinical trial NCT05648526: Neuroprotective Effects of ACTH4-10PRO8-GLY9-PRO10
Official title: Neuroprotective Effects of ACTH4-10PRO8-GLY9-PRO10 on The Ketamine-Induced Neurotoxicity In Neonatal Rats: Increased BDNF Expression And BDNF Serum Concentrations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ketamine-Induced Neurotoxicity
Keywords: ACTH4-10Pro8-Gly9-Pro10
BDNF
ketamine-induced neurotoxicity
apoptosis
Lead sponsor: Universitas Sumatera Utara
Sponsor class: OTHER
First posted: 2022-12-13
Enrollment: 42
Sex: MALE
Minimum age (years): 7
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The compound ACTH4-10Pro8-Gly9-Pro10 is a synthetic analog molecule of an adrenocorticotropic hormone (ACTH) short fragment. That is free from hormonal effects and has neuromodulatory effects. We investigate the neuroprotective effects of ACTH4-10Pro8-Gly9-Pro10 can lessen neurotoxicity against ketamine in neonatal rats by looking at BDNF expression in the cortex and hippocampus tissue as well as BDNF blood levels.

Detailed description: The compound ACTH4-10Pro8-Gly9-Pro10 is a synthetic analog molecule of a short fragment of adrenocorticotropic hormone (ACTH). It is free from hormonal effects and has neuromodulatory effects. The immune-modulating and neurotrophic activity of the drug were shown to balance the state of anti-inflammatory and trophic factors (IL-IO, TNF-a, TGF-Pl, BDNF, NGF) over proinflammatory factors (IL-Ip, IL-8, CRP, LE) to increase the anti-apoptotic defense (Bcl-2 elevation), as well as to reduce the peroxidation process (increased SOD activity).

ACTH4-10Pro8-Gly9-Pro10 also has neuromodulator characteristics to function as a neuroprotector in inhibiting the apoptotic process. Modulation by ACTH4-10Pro8-Gly9-Pro10 will increase the levels of BDNF thereby inhibiting the process of apoptosis. Based on research by Gusev and Skvortsova, ischemic stroke patients who were given ACTH4-10Pro8-Gly9-Pro10 showed increased levels of BDNF, decreased mortality, and reduced length of stay. Based on the description above, the researcher was interested in analyzing the effect of the administration of ACTH4-10Pro8-Gly9-Pro10 on ketamine neurotoxicity in neonatal rats by assessing the level of BDNF.

Eligibility criteria: Inclusion Criteria:

* Rattus norvegicus rats
* Male, seven days old, weighing 15-20 grams
* Spraque-Dawley strain, obtained from the Experimental Animal Care Unit

Exclusion Criteria:

* Animals that behave aggressively in observation by attacking other groups

Primary outcomes:
measure: BDNF Expression
timeFrame: On 6 hours after the study drug dose
measure: BDNF Serum Concentrations
timeFrame: On 6 hours after the study drug dose
Secondary outcomes:
Other outcomes:
Locations:
city: Medan
country: Indonesia
facility: Faculty of Medicine Universitas Sumatera Utara
state: Sumatera Utara
Study officials:
References:
citation: Ing C, DiMaggio C, Whitehouse A, Hegarty MK, Brady J, von Ungern-Sternberg BS, Davidson A, Wood AJ, Li G, Sun LS. Long-term differences in language and cognitive function after childhood exposure to anesthesia. Pediatrics. 2012 Sep;130(3):e476-85. doi: 10.1542/peds.2011-3822. Epub 2012 Aug 20.
citation: Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, Sprung J, Weaver AL, Schroeder DR, Warner DO. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011 Nov;128(5):e1053-61. doi: 10.1542/peds.2011-0351. Epub 2011 Oct 3.