Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers (NPY)
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:
- 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.
- To test the effect of intranasal NPY administration on mood and anxiety.
|Mood Disorder Anxiety Disorders||Drug: Low dose NPY Drug: High dose NPY Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers|
- Levels of NPY in CSF [ Time Frame: on study day 2 ]Levels of Neuropeptide Y in the cerebrospinal fluid
- Systematic Assessment of Treatment-Emergent Effects (SAFTEE) [ Time Frame: on study day 2 ]Number of participants with serious adverse events
- Appetite Scale [ Time Frame: on study day 2 ]measure in 2 hours post intranasal administration
- Post-sleep Questionnaire [ Time Frame: on study day 2 ]measure in the morning
- Quick Inventory of Depressive Symptoms (QIDS) [ Time Frame: on study day 2 ]measure in 2 hours post intranasal administration
- Profile of Mood States (POMS) [ Time Frame: on study day 2 ]measure in 2 hours post intranasal administration and on the next morning
|Study Start Date:||January 2010|
|Study Completion Date:||January 2012|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
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 (0nmol)) administered intranasally
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00748956
|United States, New York|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|Principal Investigator:||Adriana Feder, MD||Icahn School of Medicine at Mount Sinai|
|Principal Investigator:||Dennis Charney, MD||Icahn School of Medicine at Mount Sinai|