Intranasal Administration of a Prokinetic for Bowel Evacuation in Persons With SCI
Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: SCI
Intervention: IN NEO (Drug); IN NEO (Drug); IN NEO (Drug); IN NEO + IN Glycopyrrolate (Drug); IV Visit (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Department of Veterans Affairs Official(s) and/or principal investigator(s): Mark A. Korsten, MD, Principal Investigator, Affiliation: VA Medical Center, Bronx
Summary
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.
Clinical Details
Official title: Intranasal Administration of Neostigmine and Glycopyrrolate for Bowel Evacuation
Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Bowel evacuation
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
Minimum age: 18 Years.
Maximum age: 89 Years.
Gender(s): Both.
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
Locations and Contacts
VA Medical Center, Bronx, Bronx, New York 10468, United States
Additional Information
Starting date: September 2012
Last updated: July 23, 2013
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