Mood DisorderPhase 2NPYNCT00748956
Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers
A Phase 2 study testing Low dose NPY and High dose NPY in people with Mood Disorder and Anxiety Disorders, run by Dennis Charney at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 25 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Mood Disorder, Anxiety Disorders
- What is being tested?
- Low dose NPY and High dose NPY
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Jan 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai School of Medicine
New York, New York, 10029
About this study
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.
Read the 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.
- Conditions
- Mood Disorder, Anxiety Disorders
- Being tested
- Low dose NPY, High dose NPY, Placebo
- Keywords
- Mood Disorder, Anxiety Disorders
- Medical subject headings
- Mood Disorders, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose NPYDrug
Also called Neuropeptide Y
50nmol, administered intranasally
High dose NPYDrug
Also called Neuropeptide Y
100nmol administered intranasally
PlaceboDrug
placebo comparator (0nmol)) administered intranasally
| Study group | Role | What they receive |
|---|---|---|
| Low dose NPY | Experimental | Low dose, Receive 50 nmol dose of NPY Receives: Drug: Low dose NPY |
| High dose NPY | Experimental | High Dose, Receive 100 nmol dose of NPY Receives: Drug: High dose NPY |
| Placebo | Placebo comparator | Placebo comparator Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of NPY in CSF
Levels of Neuropeptide Y in the cerebrospinal fluid
Measured: on study day 2
Secondary outcomes (5)
Systematic Assessment of Treatment-Emergent Effects (SAFTEE)
Number of participants with serious adverse events
Measured: on study day 2
Appetite Scale
measure in 2 hours post intranasal administration
Measured: on study day 2
Post-sleep Questionnaire
measure in the morning
Measured: on study day 2
Quick Inventory of Depressive Symptoms (QIDS)
measure in 2 hours post intranasal administration
Measured: on study day 2
Profile of Mood States (POMS)
measure in 2 hours post intranasal administration and on the next morning
Measured: on study day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2008 (estimated)
- Study startJan 2010
- Primary completionDec 2010
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Mood DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dennis Charney
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dennis Charney, Icahn School of Medicine at Mount Sinai
- Investigators
- Adriana Feder, MD, Principal investigator, Icahn School of Medicine at Mount SinaiDennis Charney, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00748956
- Sponsor's protocol ID
- GCO 05-0986
- Other IDs
- PT050986
- Acronym
- NPY
- Status last verified
- Jul 2017
- First submitted
- 8 Sep 2008
- Last updated
- 1 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1016/s0006-3223(03)00433-5.
PubMed 14625151Morgan 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. doi: 10.1016/s0006-3223(99)00239-5.
PubMed 10807963Rasmusson 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. doi: 10.1016/s0006-3223(99)00185-7.
PubMed 10715359Rasmusson 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. doi: 10.1016/S0893-133X(97)00199-1.
PubMed 9608581Thorsell 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. doi: 10.1097/00001756-199909290-00024.
PubMed 10549813Flood 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. doi: 10.1016/0006-8993(89)91706-x.
PubMed 2611661Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004 Aug;38(4):213-24. doi: 10.1016/j.npep.2004.05.002.
PubMed 15337373Eaton K, Sallee FR, Sah R. Relevance of neuropeptide Y (NPY) in psychiatry. Curr Top Med Chem. 2007;7(17):1645-59. doi: 10.2174/156802607782341037.
PubMed 17979774Nikisch G, Agren H, Eap CB, Czernik A, Baumann P, Mathe 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. doi: 10.1017/S1461145705005158. Epub 2005 Mar 23.
PubMed 15784158
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT00748956
- Acronym / sponsor ID
- NPY / GCO 05-0986
- Conditions
- Mood Disorder, Anxiety Disorders
- Keywords
- Mood Disorder, Anxiety Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Dennis CharneyUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 9 Sep 2008 (estimated)
- Results
- Posted 17 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low dose NPY | Experimental | Drug: Low dose NPYLow dose, Receive 50 nmol dose of NPY |
| High dose NPY | Experimental | Drug: High dose NPYHigh Dose, Receive 100 nmol dose of NPY |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo comparator |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low dose NPYAlso: Neuropeptide Y50nmol, administered intranasally | Drug | Low dose NPY |
| High dose NPYAlso: Neuropeptide Y100nmol administered intranasally | Drug | High dose NPY |
| Placeboplacebo comparator (0nmol)) administered intranasally | Drug | Placebo |
Primary outcome
Levels of NPY in CSF
Time frame: on study day 2
Levels of Neuropeptide Y in the cerebrospinal fluid
5 secondary outcomes
Systematic Assessment of Treatment-Emergent Effects (SAFTEE)
Time frame: on study day 2
Appetite Scale
Time frame: on study day 2
Post-sleep Questionnaire
Time frame: on study day 2
Quick Inventory of Depressive Symptoms (QIDS)
Time frame: on study day 2
Profile of Mood States (POMS)
Time frame: on study day 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14625151Morgan 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. doi: 10.1016/s0006-3223(03)00433-5.
- Background: PubMed 10807963Morgan 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. doi: 10.1016/s0006-3223(99)00239-5.
- Background: PubMed 10715359Rasmusson 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. doi: 10.1016/s0006-3223(99)00185-7.
- Background: PubMed 9608581Rasmusson 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. doi: 10.1016/S0893-133X(97)00199-1.
- Background: PubMed 10549813Thorsell 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. doi: 10.1097/00001756-199909290-00024.
- Background: PubMed 2611661Flood 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. doi: 10.1016/0006-8993(89)91706-x.
- Background: PubMed 15337373Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004 Aug;38(4):213-24. doi: 10.1016/j.npep.2004.05.002.
- Background: PubMed 17979774Eaton K, Sallee FR, Sah R. Relevance of neuropeptide Y (NPY) in psychiatry. Curr Top Med Chem. 2007;7(17):1645-59. doi: 10.2174/156802607782341037.
- Background: PubMed 15784158Nikisch G, Agren H, Eap CB, Czernik A, Baumann P, Mathe 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. doi: 10.1017/S1461145705005158. Epub 2005 Mar 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adriana Feder, MD principal investigator
Icahn School of Medicine at Mount Sinai
Dennis Charney, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low dose NPY and High dose NPY in people with Mood Disorder and Anxiety Disorders, run by Dennis Charney at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levels of NPY in CSF (time frame: on study day 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00748956, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2017.