Neuroprotective Effects of ACTH4-10PRO8-GLY9-PRO10

Sponsor

Universitas Sumatera Utara (Other)

Overall Status

Completed

CT.gov ID

NCT05648526

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

14.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ketamine-Induced Neurotoxicity	Drug: ACTH4-10Pro8-Gly9-Pro10 Drug: Ketamine	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

Neuroprotective Effects of ACTH4-10PRO8-GLY9-PRO10 on The Ketamine-Induced Neurotoxicity In Neonatal Rats: Increased BDNF Expression And BDNF Serum Concentrations

Actual Study Start Date :

Aug 1, 2021

Actual Primary Completion Date :

Sep 30, 2021

Actual Study Completion Date :

Oct 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ACTH4-10PRO8-GLY9-PRO10 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.	Drug: ACTH4-10Pro8-Gly9-Pro10 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
Active Comparator: ketamine 40 mg/kg BW subcutaneously ketamine results in impaired brain function associated with neuroapoptosis injury in the immature brain.	Drug: Ketamine negative-positive control (ketamine 40 mg/kg BW subcutaneously)

Arm

Intervention/Treatment

Experimental: ACTH4-10PRO8-GLY9-PRO10

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.

Drug: ACTH4-10Pro8-Gly9-Pro10

Active Comparator: ketamine 40 mg/kg BW subcutaneously

ketamine results in impaired brain function associated with neuroapoptosis injury in the immature brain.

Drug: Ketamine

negative-positive control (ketamine 40 mg/kg BW subcutaneously)

Outcome Measures

Primary Outcome Measures

BDNF Expression [On 6 hours after the study drug dose]
a protein that, in humans, is encoded by the BDNF gene
BDNF Serum Concentrations [On 6 hours after the study drug dose]
a protein that, in humans, is encoded by the BDNF gene

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Days to 7 Days

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Faculty of Medicine Universitas Sumatera Utara	Medan	Sumatera Utara	Indonesia	20155

Sponsors and Collaborators

Universitas Sumatera Utara

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

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.

Responsible Party:

Raka Jati Prasetya, Doctor, Universitas Sumatera Utara

ClinicalTrials.gov Identifier:

NCT05648526

Other Study ID Numbers:

Intervention

First Posted:

Dec 13, 2022

Last Update Posted:

Dec 13, 2022

Last Verified:

Dec 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Raka Jati Prasetya, Doctor, Universitas Sumatera Utara

ACTH4-10Pro8-Gly9-Pro10

BDNF

ketamine-induced neurotoxicity

apoptosis

Additional relevant MeSH terms:

Neurotoxicity Syndromes

Ketamine

Study Results

No Results Posted as of Dec 13, 2022