Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers (NPY)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dennis Charney, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00748956
First received: September 8, 2008
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

There is growing evidence that neuropeptides act as neuronal messengers in the brain and have diverse functions that may include the regulation of mood and behavior. For example, neuropeptide Y (NPY) is thought to play a role in the adaptive stress response. The therapeutic application of neuropeptides for psychiatric disorders has been limited by difficult and unreliable penetration of the blood-brain barrier (BBB). However, recent data suggest that intranasal administration may provide a means of effectively delivering some of these neuropeptides to the brain. Thus far it is unclear if this is the case for NPY. The aims of this project are:

  1. To evaluate, in 15 healthy male volunteers aged 25-45, the effect of intranasal NPY administration (0, 50 and 100 nmol) on its levels in cerebrospinal fluid (CSF), measured by means of lumbar puncture using an intraspinal catheter between L4 and L5, and in plasma, measured using an intravenous catheter in the forearm. One of the three treatments will be administered to each participant in a double-blind fashion. The 0 nmol condition will serve as the placebo control.
  2. To test the effect of intranasal NPY administration on mood and anxiety.

Condition Intervention Phase
Mood Disorder
Anxiety Disorders
Drug: Low dose NPY
Drug: High dose NPY
Drug: Placebo
Phase 2

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:


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 2 ] [ Designated as safety issue: No ]
    samples collected at 10 min and 20 minute intervals in 2 hours post intranasal administration


Secondary Outcome Measures:
  • Systematic Assessment of Treatment-Emergent Effects (SAFTEE) [ Time Frame: on study day 2 ] [ Designated as safety issue: Yes ]
    measure in 2 hours post intranasal administration

  • Appetite Scale [ Time Frame: on study day 2 ] [ Designated as safety issue: No ]
    measure in 2 hours post intranasal administration

  • Post-sleep questionnaire [ Time Frame: on study day 2 ] [ Designated as safety issue: No ]
    measure in the morning

  • Quick Inventory of Depressive Symptoms (QIDS) [ Time Frame: on study day 2 ] [ Designated as safety issue: No ]
    measure in 2 hours post intranasal administration

  • Profile of Mood States (POMS) [ Time Frame: on study day 2 ] [ Designated as safety issue: No ]
    measure in 2 hours post intranasal administration and on the next morning


Enrollment: 10
Study Start Date: January 2010
Study Completion Date: January 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose NPY
Low dose, Receive 50 nmol dose of NPY
Drug: Low dose NPY
50nmol, administered intranasally
Other Name: Neuropeptide Y
Experimental: High dose NPY
High Dose, Receive 100 nmol dose of NPY
Drug: High dose NPY
100nmol administered intranasally
Other Name: Neuropeptide Y
Placebo Comparator: Placebo
Placebo comparator
Drug: Placebo
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:

Responsible Party: Dennis Charney, Dean, 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: December 10, 2012
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 April 15, 2014