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Impact of Hot Flashes on Sleep and Mood Disturbance

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hadine Joffe, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01116401
First received: May 3, 2010
Last updated: April 5, 2013
Last verified: April 2013
History of Changes
  Purpose

We plan to enroll 60 healthy, non-pregnant premenopausal women age 18-45 who do not have hot flashes (in order to have 30 women complete all study procedures) in a trial investigating the impact of hot flashes developed in response to an injection of a GnRH agonist, leuprolide (brand name: Lupron) on sleep disruption and mood. This study is designed to mimic the menopause transition. Based on previous studies, we expect that 2/3 of the women will develop hot flashes, naturally dividing participants into two groups: + hot flashes and no hot flashes. We will collect data on sleep disruption and mood changes to compare differences between the + hot flashes group and the group of women who do not develop hot flashes on leuprolide.

Specific Aim 1: To determine the effects of hot flashes on sleep using a model of induced hot flashes in pre-menopausal women.

Hypothesis 1a: Hot flashes worsen objectively measured sleep

Hypothesis 1b: Exposure to hot flashes leads to the perception of poor sleep quality

Specific Aim 2: To identify the relative effects of hot flashes and sleep disruption on mood using a model of induced hot flashes in premenopausal women.

Hypothesis 2a: Objectively measured sleep disturbance has a greater effect than hot flashes on mood

Hypothesis 2b: Perception of poor sleep correlates with negative mood

Exploratory Aim: To establish the feasibility of identifying specific genetic polymorphisms for genes involved in the estrogen pathway and the development of hot flashes.


Condition Intervention
Menopause
Depression
Hot Flashes
 Drug: Leuprolide

Study Type: Interventional
Study Design: Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Impact of Experimentally Induced Hot Flashes on Sleep and Mood Disturbance

Resource links provided by NLM:

MedlinePlus related topics: Depression Menopause
U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in sleep efficiency from pre- to post-GnRH agonist administration [ Time Frame: Two PSG studies at baseline and two PSG studies at study end, 4 weeks after GnRH agonist administration ] [ Designated as safety issue: No ]
    Sleep efficiency will be calculated by averaging the two PSG studies at each time point.


Secondary Outcome Measures:
  • Average daily number of subjectively reported hot flashes (hot flash diary) [ Time Frame: 4th week after GnRH agonist is given ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: October 2009
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GnRH Agonist Injection
We will be administering an injection of leuprolide acetate (a GnRH agonist) to all participants.
 Drug: Leuprolide

Leuprolide acetate 3.75-mg intramuscular injection

Leuprolide is a widely used GnRH agonist. Leuprolide is indicated for treatment of endometriosis, uterine fibroids, precocious puberty, and prostate cancer, and is used off-label for in-vitro fertilization and premenstrual syndrome. In this protocol, leuprolide will be administered at a dose routinely used for treatment of endometriosis and uterine fibroids in women.

Leuprolide can induce amenorrhea for 2-3 months after a depot injection is given. However, unpredictable menstrual bleeding and spotting can occur during this time period. Menstrual-cycle patterns will be monitored closely during the study. Although long-term administration of any GnRH agonist (i.e., >6 months) is associated with bone loss, bone effects are not expected in this protocol because GnRH agonist therapy will be used for only one month.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women 18-45 years old
  • Premenopausal, defined as regular monthly menstrual cycles (every 25-35-days) for the past 6 months and corroborated by a mid-luteal phase progesterone of > 3 ng/ml
  • Willingness to use barrier methods of contraception during study and after completion of study until menses resume
  • Good general health with normal hemoglobin, prolactin, TSH, liver function tests (SGOT, SGPT, bilirubin) and renal function tests (BUN, creatinine, alkaline phosphatase)

Exclusion Criteria:

  • Pregnancy, as determined by serum HCG at screening visit and immediately preceding (day before or day of) GnRH agonist administration, or currently breastfeeding.
  • Hot flushes, as determined subjectively (7-day hot flash diary) and objectively (24-hour skin-conductance monitoring
  • Mid-luteal phase progesterone <3ng/mL
  • Clinically significant abnormalities in screening blood tests.
  • BMI > 35 kg/m2
  • Previously diagnosed osteoporosis or osteopenia
  • Clinically significant depressive symptoms (Montgomery-Asberg Depression Rating Scale (MADRS) score > 10)
  • Psychiatric illness, as defined by clinical interview and the Mini-International Neuropsychiatric Interview (MINI).
  • Sleep apnea or periodic limb movement of sleep (PLMS) either diagnosed previously or on a screening polysomnography (PSG) study.
  • Contraindication, hypersensitivity, or previous allergic reaction to GnRH agonists
  • Current or recent (one month) use of centrally active medications (antidepressants, anxiolytics, hypnotics, or the anticonvulsant gabapentin.
  • Current or recent (3 months) use of systemic hormone medications
  • Night shift workers
  • Current or recent (one month) over-the-counter (OTC) medications that may affect hot flashes, sleep, or mood (eg diphenhydramine, St. John's Wort, Black Cohosh, and other phytoestrogen supplements)
  • Abnormal vaginal bleeding
  • History of any medical diseases that may put subject at risk when treated with study medication. These include a history of thrombo-embolism or cardiovascular disease, congestive heart failure or other conditions requiring sodium restriction, spinal cord compression, metastatic vertebral lesions, memory disorders, urinary tract obstruction or history of liver, kidney, pulmonary, or metabolic disease that may put subject at risk when treated with study medication.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01116401

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Hadine Joffe, MD
Investigators
Principal Investigator: Hadine Joffe, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Hadine Joffe, MD, Director of Research at the Center for Women's Mental Health, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01116401     History of Changes
Other Study ID Numbers: 2009-P-001557
Study First Received: May 3, 2010
Last Updated: April 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Hot Flashes
Sleep disturbance
Lupron
Menopause

Additional relevant MeSH terms:
Depression
Depressive Disorder
Hot Flashes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Signs and Symptoms
Deslorelin
Leuprolide
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013