Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers - Full Text View

Sponsor:	Dennis Charney
Information provided by (Responsible Party):	Dennis Charney, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:	NCT00748956

Purpose

The mood and anxiety disorders have been a prevailing health issue for the population and society nowadays. New treatments for mental disorders are being explored and studied while the currently available treatments have high non-response and relapse rate. Neuropeptide Y, a peptide that has been shown to have anxiolytic and antidepressant effects in animal and human studies, has been under investigation for its therapeutic applications in human. The current therapeutic applications for mental disorders have been limited by the blood-brain barrier (BBB) that prevents big molecules from entering the central nervous system. However, studies have shown that intranasal administration may deliver big molecules directly to the brain via a nose-to-brain route, making the direct therapeutic application of neuropeptides on the brain possible. Our study aims to investigate the intranasal administration of neuropeptide Y in healthy men. We administer neuropeptide Y intranasally and measure its level in the cerebrospinal fluid, which would indicate its entry into the central nervous system. We plan to recruit 10 healthy men (age 25-45) for the study. Depending on the initial feasibility and tolerability in healthy volunteers, future protocols will examine the effect of intranasal neuropeptide Y administration in patients with mood and anxiety disorders such as depression, PTSD, panic disorder, and social anxiety disorder.

Condition	Intervention	Phase
Mood Disorder Anxiety Disorders	Drug: Neuropeptide Y	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-availability Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers

Resource links provided by NLM:

MedlinePlus related topics: Anxiety Mental Disorders

U.S. FDA Resources

Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:

Levels of NPY in CSF and plasma [ Time Frame: on study day 1 ] [ Designated as safety issue: No ]
samples collected at 10 min and 20 minute intervals during a 2 hour study procedure

Secondary Outcome Measures:

Systematic Assessment of Treatment-Emergent Effects (SAFTEE) [ Time Frame: on study day 1 ] [ Designated as safety issue: Yes ]
measure completed during a 2 hour study procedure
Appetite Scale [ Time Frame: on study day 1 ] [ Designated as safety issue: No ]
measure completed during a 2 hour study procedure
Post-sleep questionnaire [ Time Frame: on study day 2 ] [ Designated as safety issue: No ]
measure completed at 24 hours post procedure
Quick Inventory of Depressive Symptoms (QIDS) [ Time Frame: on study day 1 ] [ Designated as safety issue: No ]
measure completed during a 2 hour study procedure
Quick Inventory of Depressive Symptoms (QIDS) [ Time Frame: on study day 2 ] [ Designated as safety issue: No ]
measure completed at 24 hours post procedure
Profile of Mood States (POMS) [ Time Frame: on study day 1 ] [ Designated as safety issue: No ]
measure completed during a 2 hour study procedure
Profile of Mood States (POMS) [ Time Frame: on study day 2 ] [ Designated as safety issue: No ]
measure completed at 24 hours post procedure

Estimated Enrollment:	15
Study Start Date:	January 2010
Estimated Study Completion Date:	January 2012
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Low dose Low dose, Receive 50 nmol dose of NPY	Drug: Neuropeptide Y 50nmol, administered intranasally
Experimental: High dose High Dose, Receive 100 nmol dose of NPY	Drug: Neuropeptide Y 100nmol administered intranasally
Placebo Comparator: Placebo Placebo comparator	Drug: Neuropeptide Y placebo comparator (0nmol)) administered intranasally

Detailed Description:

There is growing evidence that neuropeptides, including neuropeptide Y (NPY), act as neuronal messengers in the brain and have diverse neurobehavioral functions. Their therapeutic application for psychiatric disorders has been limited, however, by difficult and unreliable penetration of the blood-brain barrier (BBB). The BBB has prevented the use of many therapeutic agents for treating central nervous system (CNS) disorders. Several molecules have successfully been administered through intranasal delivery, however, thanks to the unique connection that the nerves involved in sensing odors and chemicals provide between the CNS and its environment.

NPY, the most abundant peptide in the mammalian brain, is co-localized with norepinephrine in sympathetic nerve fibers and has been of longstanding interest to our research group (Morgan et al., 2002; Morgan et al., 2003; Morgan et al., 2001; Morgan et al., 2000; Rasmusson et al., 2000; Rasmusson et al., 1998) because of its potential role in modulating mood and anxiety. NPY has been implicated as factor in the adaptive stress response (Thorsell et al., 1999), and has been shown to impact the consolidation of fear-related memories after shock (Flood et al., 1989). Clinically, lower plasma NPY levels have been correlated with greater psychological distress, increased symptoms of dissociation, and poorer performance among active duty military personnel. Acute stress in humans has been found to elicit NPY release, in a manner parallel to the changes in cortisol and norepinephrine that are usually seen, with a blunting of the plasma NPY response in response to yohimbine (Morgan et al., 2002). Baseline NPY levels in combat veterans with PTSD are reduced compared to healthy non-traumatized individuals (Rasmusson et al., 2000). Another study found that repeated exposure to traumatic stress, rather than the presence of PTSD or PTSD-type symptoms, is associated with a reduction in baseline plasma NPY (Morgan et al., 2003). A recent report found deceased CSF concentrations of NPY in patients with treatment resistant unipolar major depression (Heilig et al 2004). In summary, there has been suggestion from studies in patients with anxiety and mood disorders as well as healthy volunteers of an abnormal regulation of this peptide.

In this study, we will evaluate intranasal administration of NPY in healthy male volunteers ages 25-45 using a specialized delivery device. Pending the initial feasibility and tolerability in healthy volunteers, future protocols will examine the effect of intranasal NPY administration in patients with disorders such as PTSD, major depression, panic disorder, and social anxiety disorder.

Eligibility

Ages Eligible for Study:	25 Years to 45 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Men aged 25-45.
No history of Axis I disorder as defined in the DSM-IV other than past nicotine abuse or dependence or adjustment disorder.

Exclusion Criteria:

Nicotine or caffeine abuse or dependence within the preceding 3 months.
History or complaint of nasal disorders or allergies.
Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic.
Significant obesity (BMI > 30), scoliosis, spinal stenosis or a history of lumbosacral laminectomy.
Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG.
Current use of any medications that have effects on CNS function.
Prior sinonasal surgery, or significant nasal polyps as determined by nasal endoscopy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00748956

Locations

United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029

Sponsors and Collaborators

Dennis Charney

Investigators

Principal Investigator:	Adriana Feder, MD	Mount Sinai School of Medicine
Principal Investigator:	Dennis Charney, MD	Mount Sinai School of Medicine

More Information

Publications:

Morgan CA 3rd, Rasmusson AM, Winters B, Hauger RL, Morgan J, Hazlett G, Southwick S. Trauma exposure rather than posttraumatic stress disorder is associated with reduced baseline plasma neuropeptide-Y levels. Biol Psychiatry. 2003 Nov 15;54(10):1087-91.

Morgan CA 3rd, Wang S, Southwick SM, Rasmusson A, Hazlett G, Hauger RL, Charney DS. Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biol Psychiatry. 2000 May 15;47(10):902-9.

Rasmusson AM, Hauger RL, Morgan CA, Bremner JD, Charney DS, Southwick SM. Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD. Biol Psychiatry. 2000 Mar 15;47(6):526-39.

Rasmusson AM, Southwick SM, Hauger RL, Charney DS. Plasma neuropeptide Y (NPY) increases in humans in response to the alpha 2 antagonist yohimbine. Neuropsychopharmacology. 1998 Jul;19(1):95-8.

Thorsell A, Carlsson K, Ekman R, Heilig M. Behavioral and endocrine adaptation, and up-regulation of NPY expression in rat amygdala following repeated restraint stress. Neuroreport. 1999 Sep 29;10(14):3003-7.

Flood JF, Baker ML, Hernandez EN, Morley JE. Modulation of memory processing by neuropeptide Y varies with brain injection site. Brain Res. 1989 Nov 27;503(1):73-82.

Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004 Aug;38(4):213-24. Review.

Eaton K, Sallee FR, Sah R. Relevance of neuropeptide Y (NPY) in psychiatry. Curr Top Med Chem. 2007;7(17):1645-59. Review.

Nikisch G, Agren H, Eap CB, Czernik A, Baumann P, Mathé AA. Neuropeptide Y and corticotropin-releasing hormone in CSF mark response to antidepressive treatment with citalopram. Int J Neuropsychopharmacol. 2005 Sep;8(3):403-10. Epub 2005 Mar 23.

Responsible Party:	Dennis Charney, MD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:	NCT00748956 History of Changes
Other Study ID Numbers:	GCO-05-0986, PT050986
Study First Received:	September 8, 2008
Last Updated:	November 10, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:

Mood Disorder
Anxiety Disorders

Additional relevant MeSH terms:

Anxiety Disorders
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on February 09, 2012