Effects of Intranasal Nerve Growth Factor for Acute Ischemic Stroke

Stroke remains one of the leading causes of death and adult disability worldwide. Yet, currently, the only accepted treatment for acute ischemic stroke(AIS) is recanalization of occluded arteries. Thrombolysis with tissue plasminogen activator, limited by its narrow therapeutic time window and the concern of hemorrhagic complication, is still uncommon in use. The other approach is to try to impede the ischemic cascade by targeting various components of the cascade that are deemed to be of importance, namely, a neuroprotection strategy.

Nerve growth factor (NGF) plays extensive roles in preventing ischemic injury. Besides that, it is also involved in neurogenesis of the central nervous system (CNS). In addition, the levels of NGF protein and messenger RNA significantly decreased in the CNS at the first few hours and returned to normal levels several days later after middle cerebral artery occlusion (MCAO) in animal models. These observed results suggested that NGF was demanded in ischemic brain injury, but endogenous NGF is insufficient for the requirement and delivering exogenous ones will be blocked in entering into the CNS by the blood-brain barrier (BBB). Intracerebroventricular or intracerebral injection of NGF or grafting of NGF-producing cells may be less practicable due to invasiveness and safety concerns.

Intranasal (IN) administration is a noninvasive and acceptable delivery strategy for drugs bypassing BBB and can deliver NGF to the CNS, which has been proved to show neuroprotective effects on brain injury.

The effects of intranasal NGF in human ischemic stroke is still controversial that need further evaluation.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Nerve Growth Factors; Drug: normal saline

Detailed Description

The proposed study is a randomized, double-blind, placebo-controlled trail of NGF, starting between 24 to 72 hours post acute ischemic stroke, continuing for 2 weeks.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Department of Neurology, Jinling Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18years;
2. Acute ischemic stroke consistent within 72 hours;
3. Written informed consent from patient or surrogate, if unable to provide consent.

Exclusion Criteria:

1. Premorbid mRS ≥ 3 points;
2. Currently in pregnant or lactating;
3. Allergy to NGF;
4. Current participation in another investigation drug or device study;
5. Life expectancy less than 1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IN-NGF group; Patients who underwent acute ischemic stroke will be chosen to receive NGF randomly	Drug: Nerve Growth Factors; the experimental group patients will receive NGF 20ug/d intranasally for 2 weeks
Placebo Comparator: Control group; Patients who underwent acute ischemic stroke will be chosen to receive normal saline randomly	Drug: normal saline; The Placebo Comparator group patients will receive nomral saline 20ug/d intranasally for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
a favorable neurological function	The primary outcome is determined as a favorable neurological function which is defined as Modified Rankin Scale(mRS) score of 0-3	at 90 days post-treatment

Collaborators and Investigators

• Sponsor: Jinling Hospital, China
• Investigators: Study Chair: Xinfeng Liu, MD, Department of Neurology, Jinling Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 29, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Intranasal; Nerve Growth Factor; Acute Ischemic stroke; Neurological Function
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: NGF-ischemic stroke

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No