Effects of a Kappa Agonist on Hot Flashes in Menopausal Women

Studies suggest that kappa agonists (KA) and peripherally restricted kappa agonists (PRKAs) may affect thermoregulation. This pilot study has the aim to establish proof of concept regarding efficacy of an oral kappa agonist (KA) for the treatment of menopausal hot flashes.

Study Overview

• Status: Completed
• Conditions: Treatment of Menopausal Hot Flashes
• Intervention / Treatment: Other: Placebo; Drug: Standard Dose Kappa Agonist; Drug: Half Dose Kappa Agonist

Detailed Description

To establish proof of concept regarding efficacy of an oral kappa agonist (KA), Pentazocine/ Naloxone 50/0.5 mg, for the treatment of menopausal hot flashes.

To gather data in support of a future proposal to study the safety and efficacy of a PRKA, a type of KA, for amelioration of menopausal hot flashes.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Healthy women 45-60 years of age; 12 months amenorrhea
2. Documentation of > 8 moderate to severe, daily hot flashes during one week of baseline monitoring using daily diaries
3. Availability of a family member or friend to drive participant home following clinic visits

Exclusion Criteria:

1. Use of hormonal prescription medication or supplements for vasomotor symptoms (VMS)
2. Use of narcotics
3. Use of SSRI (selective serotonin reuptake inhibitor)/SNRI (serotonin-norepinephrine reuptake inhibitors), gabapentin, MAOI (monoamine oxidase inhibitor), anti-epileptics, sedatives
4. History of polycystic ovarian syndrome or hirsutism
5. Current history of depression
6. Any chronic or acute medical illnesses including renal, hepatic, pulmonary diseases, or seizures
7. Substance abuse
8. Severe corn allergy
9. Known allergic reaction to pentazocine or naloxone
10. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
11. Hysterectomy
12. Use of anticholinergic medications
13. Lactating or pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Cornstarch, National Formulary	Other: Placebo
Experimental: Standard Dose Kappa Agonist; Pentazocine/Naloxone 50/0.5 mg	Drug: Standard Dose Kappa Agonist; Other Names: Pentazocine/Naloxone 50/0.5 mg
Experimental: Half Dose Kappa Agonist; Pentazocine/Naloxone 25/0.25 mg	Drug: Half Dose Kappa Agonist; Other Names: Pentazocine/Naloxone 25/0.25 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hot Flashes	Objectively measured hot flash frequency by changes in skin conductance over 8 hours on 3 separate study visits 3-14 days apart.	1-4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjectively measured hot flashes	Self-reported diary documentation of time and occurence of hot flashes and intensity of hot flashes over 8 hours on 3 separate study visits 3-14 days apart.	1-4 weeks
Change in Serum Leutinizing Hormone	Serum collected at each visit baseline (before administration of treatment) and at 20-minute intervals over 8 hours on 3 separate study visits 3-14 days apart.	1-4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Follicle Stimulating Hormone	Baseline (1st visit) single time point	Baseline only
Serum Estradiol	Baseline (1st visit) single time point only.	Baseline only

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute on Aging (NIA); National Center for Complementary and Integrative Health (NCCIH); National Center for Advancing Translational Sciences (NCATS); Office of Research on Women's Health (ORWH)
• Investigators: Principal Investigator: Susan D Reed, MD, MPH, University of Washington

Publications and helpful links

General Publications

• Oakley AE, Steiner RA, Chavkin C, Clifton DK, Ferrara LK, Reed SD. kappa Agonists as a novel therapy for menopausal hot flashes. Menopause. 2015 Dec;22(12):1328-34. doi: 10.1097/GME.0000000000000476.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 21, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): July 1, 2015
• Last Update Submitted That Met QC Criteria: June 29, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: menopause; hot flashes; kappa agonist
• Additional Relevant MeSH Terms: Hot Flashes; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Narcotic Antagonists; Naloxone; Pentazocine
• Other Study ID Numbers: 43952-B; GYN-01-2012 (Other Identifier: University of Washington)