Intranasal Administration of a Prokinetic for Bowel Evacuation in Persons With SCI - Full Text View

Sponsor:	Department of Veterans Affairs
Information provided by (Responsible Party):	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00855283

Purpose

DWE (difficulty with evacuation) is a common and an important quality of life issue after spinal cord injury. Not only is the management DWE time-consuming and unpleasant, but the results are often suboptimal in terms of complications such as incontinence and impaction. Bowel care regimens after spinal cord injury have not changed in any significant fashion in many years. The usual strategies for attaining bowel evacuation involve dietary manipulation (e.g., high fiber diets and hydration), thrice weekly laxative administration (senna and cascara) and thrice weekly anorectal instillation of cathartics (enemas and suppositories). Bowel care can be quite time consuming (greater than 2 hours in many instances) and may also require extensive nursing care. Finally, incomplete evacuation could contribute to fecal incontinence that has significant morbidity in these patients.

In preliminary studies performed at the JJPVAMC, IV, IM, and subcutaneous injection of neostigmine combined with glycopyrrolate were demonstrated to be highly effective to promote bowel evacuation in the SCI population. In an effort to provide a more realistic administration of this procedure, we propose to test the intranasal spray injection of neostigmine and glycopyrrolate for safety and efficacy.

Condition	Intervention	Phase
SCI	Drug: IN NEO Drug: IN NEO + IN Glycopyrrolate Drug: IV Visit	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Intranasal Administration of Neostigmine and Glycopyrrolate for Bowel Evacuation

Resource links provided by NLM:

Drug Information available for: Neostigmine Methylsulfate Phenylephrine Neostigmine Phenylephrine hydrochloride Neostigmine bromide Glycopyrrolate Oxymetazoline Oxymetazoline hydrochloride

U.S. FDA Resources

Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:

Bowel evacuation [ Time Frame: <60 min ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	February 2007
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 SCI	Drug: IN NEO 20 mg Neostigmine via intranasal and sublingual administration Drug: IN NEO 40 mg Neostigmine via intranasal administration Drug: IN NEO 60 mg Neostigmine via intranasal administration Drug: IN NEO + IN Glycopyrrolate Intranasal or sublingual Neostigmine (at effective dose: 20, 40, or 60 mg) + 4-12 mg intranasal or sublingual Glycopyyrolate Drug: IV Visit 2mg NEO and .4mg GLY given intravenously to see if the subject responds to the intervention. If they respond, then they will proceed to the IN portion of the study.

Arms

Assigned Interventions

Experimental: 1

SCI

Drug: IN NEO

20 mg Neostigmine via intranasal and sublingual administration

Drug: IN NEO

40 mg Neostigmine via intranasal administration

Drug: IN NEO

60 mg Neostigmine via intranasal administration

Drug: IN NEO + IN Glycopyrrolate

Intranasal or sublingual Neostigmine (at effective dose: 20, 40, or 60 mg) + 4-12 mg intranasal or sublingual Glycopyyrolate

Drug: IV Visit

2mg NEO and .4mg GLY given intravenously to see if the subject responds to the intervention. If they respond, then they will proceed to the IN portion of the study.

Detailed Description:

We have been studying the effects of spinal cord injury on the bowel for over ten years. Our data suggests that one of the fundamental consequences of spinal cord injury is a slowing of intestinal peristaltic activity, most likely as a result of down regulation of parasympathetic neural pathways. Furthermore, measures that increase parasympathetic stimulation to the bowel result in bowel evacuation and improve bowel care. In this respect, significant acute effects have been demonstrated after the intravenous administration of the cholinergic agent neostigmine (Am J Gastro 100:1560-5, 2005). Long term efficacy has also been shown using intramuscular administration of neostigmine (Gastro 128:P258, 2005). Subcutaneous administration of neostigmine is in progress at this time. Bowel evacuation also is facilitated by subcutaneous administration but often requires a second dose (30 minutes after the first). This observation is likely due to a decreased rate of absorption from this tissue compartment and a correspondingly lower peak level of neostigmine (vide infra). Given the potential cardiopulmonary toxicity of neostigmine (bradycardia and bronchoconstriction), neostigmine was administered in these studies in combination with the anticholinergic agent glycopyrrolate. We have reported that the latter selectively blocks the cardiopulmonary side effects of neostigmine without significantly decreasing the prokinetic peristaltic response. In summary, our data to date indicates that the combined administration of neostigmine and glycopyrrolate is safe after spinal cord damage and it results in predicable and prompt bowel evacuation.

Eligibility

Ages Eligible for Study:	18 Years to 89 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Incomplete or complete SCI
Tetraplegia or paraplegia
Males or females
Age 18 (no upper age limit)
Excess time for bowel evacuation (> 60 minutes per bowel training session)

Exclusion Criteria:

Persons with SCI who do not require do not require additional bowel care or have "normal bowel function"
Known hypersensitivity to neostigmine or glycopyrrolate
History of mechanical obstruction of the intestine or urinary tract.
Myocardial infarction within less than 6 months of trial.
Hemodynamic instability
Potential for pregnancy. (Women who are sexually active and of childbearing potential (i.e. not surgically sterile or at least 2 year postmenopausal) must be have a negative serum pregnancy test and to have utilized one of the following methods of contraception prior to screening: barrier (condom, diaphragm with spermicide) intrauterine device, or tubal ligation beginning at least 30 days prior; hormonal (oral, injectable, transdermal, or implanted) beginning at least 3 months prior; or vasectomized partner for at least the prior 6 months. Subjects must agree to maintain these contraceptive methods through the completion of the study.)
Lactating/nursing females
Patients who develop significant bradycardia (HR<42 bpm) or other significant anticholinergic symptoms (e.g., severe cramps, dry mouth, etc.) any time during the study will be discontinued.
Concurrent participation in other clinical trials (within 30 days).
Use of concurrent medications that affect cardiac output (e.g. tricyclics, beta blockers, etc.)
Fluctuating use of concurrent medications (should be stable for 3-4 weeks before and no changes anticipated throughout the study).
History of reduced cardiac output (via history and ECG) in addition to myocardial infarction and hemodynamic instability.
Concurrent history of peripheral vascular disease, kidney disease, etc.
Asthma or other broncho-constrictive disorders.
Hemoglobin level < 12 g/dL

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00855283

Locations

United States, New York
VA Medical Center, Bronx
Bronx, New York, United States, 10468

Sponsors and Collaborators

Department of Veterans Affairs

Investigators

Principal Investigator:

Mark A. Korsten, MD

VA Medical Center, Bronx

More Information

No publications provided

Responsible Party:	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00855283 History of Changes
Other Study ID Numbers:	B4162C-2, KOR-11-018
Study First Received:	March 2, 2009
Last Updated:	January 12, 2012
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Glycopyrrolate
Neostigmine
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on February 09, 2012