Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers

NCT00748956 | Completed Phase 2 Results DMC

• 2 other identifiers: GCO 05-0986PT050986
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 2.To test the effect of intranasal NPY administration on mood and anxiety.

Conditions

Mood Disorder; Anxiety Disorders

Keywords

Mood Disorder; Anxiety Disorders

Outcome Measures

Primary Outcomes (1)

• Levels of NPY in CSF

  Levels of Neuropeptide Y in the cerebrospinal fluid

  on study day 2

Secondary Outcomes (5)

• Systematic Assessment of Treatment-Emergent Effects (SAFTEE)

  on study day 2

• Appetite Scale

  on study day 2

• Post-sleep Questionnaire

  on study day 2

• Quick Inventory of Depressive Symptoms (QIDS)

  on study day 2

• Profile of Mood States (POMS)

  on study day 2

Study Arms (3)

Low dose NPY

EXPERIMENTAL

Low dose, Receive 50 nmol dose of NPY

Drug: Low dose NPY

High dose NPY

EXPERIMENTAL

High Dose, Receive 100 nmol dose of NPY

Drug: High dose NPY

Placebo

PLACEBO COMPARATOR

Placebo comparator

Drug: Placebo

Interventions

Low dose NPY DRUG

50nmol, administered intranasally

Also known as: Neuropeptide Y

Low dose NPY

High dose NPY DRUG

100nmol administered intranasally

Also known as: Neuropeptide Y

High dose NPY

Placebo DRUG

placebo comparator (0nmol)) administered intranasally

Placebo

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dennis Charney: lead

Study Sites (1)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Publications (9)

• 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.

  PMID: 14625151 BACKGROUND

• 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. doi: 10.1016/s0006-3223(99)00239-5.

  PMID: 10807963 BACKGROUND

• 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. doi: 10.1016/s0006-3223(99)00185-7.

  PMID: 10715359 BACKGROUND

• 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. doi: 10.1016/S0893-133X(97)00199-1.

  PMID: 9608581 BACKGROUND

• 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. doi: 10.1097/00001756-199909290-00024.

  PMID: 10549813 BACKGROUND

• 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. doi: 10.1016/0006-8993(89)91706-x.

  PMID: 2611661 BACKGROUND

• Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004 Aug;38(4):213-24. doi: 10.1016/j.npep.2004.05.002.

  PMID: 15337373 BACKGROUND

• Eaton 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.

  PMID: 17979774 BACKGROUND

• Nikisch 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.

  PMID: 15784158 BACKGROUND

MeSH Terms

Conditions

Mood Disorders; Anxiety Disorders

Interventions

Neuropeptide Y

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Limitations and Caveats

Small sample size

Results Point of Contact

• Title: Dr. Adriana Feder
• Organization: Icahn School of Medicine at Mount Sinai

adriana.feder@mssm.edu

212-659-9145

Study Officials

• Adriana Feder, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Dennis Charney, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dean

Study Record Dates

• First Submitted: September 8, 2008
• First Posted: September 9, 2008
• Study Start: January 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2012
• Last Updated: August 1, 2017
• Results First Posted: May 17, 2017

Record last verified: 2017-07

Locations

US (1)