Bone Loss in Premenopausal Women with Depression
This study is currently recruiting patients.
Purpose
The purpose of this study is to determine whether women with major depression lose bone mass at a faster rate than women without
depression. This study will also determine if the drug alendronate can maintain or increase bone mass in premenopausal women
with major depression and osteoporosis.
Depression may be a major risk factor for osteoporosis; it is associated with abnormally elevated stress hormone levels that
may contribute to bone loss. This study will evaluate bone mass in women with depression and healthy volunteers.
Participants will undergo psychiatric, medical, dietary, and stress hormone evaluations and bone mineral density (BMD) measurements.
Participants with depression will be divided into two groups: those with normal BMD and those with low BMD. Depressed participants
with normal BMD will be compared to a control group of healthy premenopausal women with normal BMD and followed for 36 months.
Dual energy X-ray absorptiometry (DEXA) determinations will be made at months 6, 12, 24 and 36; bone turnover and endocrine
parameters of depression will be
measured every 3 to 6 months.
Participants with depression and low BMD will be randomly assigned to receive either alendronate or placebo (an inactive pill)
once a week for 24 months. Participants will receive calcium and vitamin D supplements daily. DEXA determinations will be
performed at screening, and at Months 6, 12, 18 and 24; bone turnover and endocrine parameters of depression will be measured
every 3 to 6 months.
For both groups, up to four of the visits may optimally be done as inpatient stays of two nights. All remaining visits are
as outpatients.
Condition
|
Treatment or Intervention |
Phase |
Depression Healthy Osteopenia Osteoporosis
|
Drug: Alendronate
|
Phase IV
|
MedlinePlus related topics: Bone Diseases; Depression; Osteoporosis
Study Type: Interventional
Study Design: Treatment
Official Title: The P.O.W.E.R. STUDY (Premenopause, Osteopenia/Osteoporosis, Women, Alendronate, Depression)
Further Study Details:
Expected Total Enrollment:
160
Study start: August 10, 2000
This is a 12-month study on the natural history of bone turn-over in depressed premenopausal women, ages 21 to 45 years, with
normal bone mass, and the response to treatment with alendronate in depressed premenopausal women, ages 21 to 45 with low
bone mass (as indicated by a bone mineral density (BMD) of negative 1.5 SD below peak bone mass at the spine and/or hip).
Osteopenia is defined as a BMD at the spine and/or hip that is between negative 1.5 and negative 2.5 SD; osteoporosis is
defined as a BMD that is below negative 2.5 SD at the spine and/or hip. During the initial screening, the women are evaluated
for depression. Women who meet DSM-IV diagnostic criteria for Major Depressive Disorder as indicated by a structured psychiatric
interview (SCID-IV and HAM-D), will then undergo a DEXA scan to determine BMD. Participants will be divided into four subcategories
based on BMD results. Premenopausal depressed women with normal BMD (less than negative 1 SD below the average peak bone
mass at the spine and/or hip) (Group B) will be matched by age, race, and body mass index to a control group of healthy, premenopausal,
non-depressed women with normal bone mass (Group A). Groups A and B will be followed for 12 months with DEXA determinations
every 6 months, measurements of bone turnover markers every 3 months, measurements of relevant endocrine parameters every
3 months, an exercise substudy at 0, 6, and 12 months, and collection of a DNA sample at one of the above visits.
Women with depression and low BMD (negative 1.5 SD below peak bone mass at the spine and/or hip) will enter a 12-month, placebo-controlled,
clinical trial where they will be randomized either to blind alendronate 70 mg once a week (Group C) or blind placebo once
a week (Group D). In addition to alendronate 70 mg once a week or placebo once a week, women in Groups C and D will also
receive daily 500 mg of elemental calcium and 400 IU of vitamin D. DEXA determinations will be performed at Screening, Month
0, Month 6, and Month 12. Determination of biochemical markers of bone turnover and endocrine parameters relevant to depression
will be performed at 0, 3, 6, 9 and 12 months. An exercise substudy will be performed at 0, 6, and 12 months. The collection
of a DNA sample will also be performed at one of the above visits.
Eligibility
Genders Eligible for Study:
Female
Accepts Healthy Volunteers
INCLUSION CRITERIA - DEPRESSED WOMEN:
The patient is a woman 21 to 45 years old on the date of the initial screening.
The patient is not postmenopausal.
She must be willing to practice an acceptable method of birth control, as appropriate (IUD, oral contraceptives, diaphragm,
condoms, hormonal implants/injection, with the exception of subdermal levonorgestrel, sterilization) and have a negative serum
pregnancy test at screening.
Women currently on estrogen/progestin contraceptive therapy must have been on a stable regimen of estrogen/progestin for at
least 6 months prior to enter the study.
The patient understands the procedures and the risks of the study and has been informed that, alternatively, she may freely
elect to be treated with the currently available treatments by her physician.
The patient voluntarily agrees to participate in the study.
INCLUSION CRITERIA RELATED TO THE PSYCHIATRIC STATUS:
The patient ihad at least one episode of major depression within the last 3 years (DSM-IV). In addition, the subject has a
past history (prior to the last 3 years) of at least one major depressive episode lasting more than 2 weeks.
With the exception of depression, the patient is in good health, based on medical history, physical examination, and laboratory
screening evaluation.
The patient has a physician; either a family doctor, a psychiatrist, a psychotherapist, or another qualified health care professional
who can provide medical treatment for depression. If the subject is not receiving any medical care for depression, a member
of the NIH team will help the patient identify one and will work closely with this professional during the study.
The patient can be on pharmacological antidepressant therapy, as medically indicated and prescribed by her primary physician
or health professional. It is not a requirement of this study for subjects to stop antidepressant treatment, unless it is
medically indicated for reasons such as the medication is ineffective, not well tolerated, or the patient no longer needs
such treatment. This decision will be based upon their physician's evaluation.
Patients starting a new antidepressant medication(s) should be on this treatment for 4-6 weeks prior to enrollment.
Carbamazepine, valproic acid or thyroid hormones used as adjunctive therapy for treatment of depression are allowed.
Women with a current or recent (within the past 3 years) history of alcohol or drug abuse are eligible if, in the opinion
of the principal investigator, this condition is not likely to impair patient compliance or if the participation in the study
does not pose additional risks to the subject.
INCLUSION CRITERIA RELATED TO THE BONE STATUS:
The patient has spinal anatomy suitable for dual-energy x-ray absorptiometry (DEXA) densitometry of the lumbar spine, with
no evidence of vertebral fractures in at least three vertebrae. Significant scoliosis, bony trauma, osteoarthritis, and sequelae
of orthopedic procedures that result in anatomy unsuitable for accurate bone densitometry, must be absent from the lumbar
spine.
The patient has osteopenia or osteoporosis, as indicated by a bone mineral density at the spine that is between 1.5 and 5
standard deviations below peak bone mass, or history of an osteoporotic vertebral or hip fracture. Patients whose eligibility
is based only on a prevalent vertebral fracture will have the fracture confirmed by a radiologist.
EXCLUSION CRITERIA - DEPRESSED WOMEN:
GENERAL EXCLUSION CRITERIA:
The patient is, in the opinion of the investigator, mentally or legally incapacitated such that informed consent cannot be
obtained.
Pregnancy or breast-feeding.
Menopause.
The patient plans to move within the next 12 months to a location which could impair a continued follow-up.
The patient has a history of or evidence for an illness or has significant abnormalities on prestudy clinical or laboratory
evaluations, which, in the opinion of the principal investigator, might complicate the interpretation of the data or pose
additional risk to the subject.
The patient has any of the following medical conditions: any malabsorption syndrome, significant genitourinary, renal (serum
creatinine greater than or equal to 1.6 mg/dL), hepatic, or pulmonary disease; uncontrolled hypertension; uncontrolled diabetes
mellitus; decompensated heart failure; clinically significant arrhythmias; unstable angina, any immunodeficiency syndrome
including AIDS.
The patient has received any drug of investigation within 30 days of the start of the study.
The use of subdermal levonorgestrel and similar preparations.
EXCLUSION CRITERIA RELATED TO THE PSYCHIATRIC STATUS:
The patient does not have an outside care provider for treatment of depression.
The patient is judged to be at suicidal risk, as clinically evident or indicated by a score of 4 at the Hamilton Scale, question
3 (suicide), or by reports of suicidal intent during SCID-IV interview.
The patient has a history suggesting potential for self-harm or violence towards others.
The patient currently has psychotic depression (e.g. hallucinations, delusions).
The patient has schizoaffective disorder.
Patients with a diagnosis of active anorexia nervosa, bulimia or any other eating disorder are not eligible.
Patients with a diagnosis of bipolar disorders type 1 or type 2 or any psychotic disorder other than psychotic depression
are not eligible.
Women with a current or recent (within the past 3 years) history of alcohol or drug dependence are not eligible.
EXCLUSION CRITERIA RELATED TO THE BONE STATUS OR THE USE OF ALENDRONATE:
The patient is affected by severe osteoporosis, as indicated by a history of recurrent non-traumatic fractures and/or a BMD
value which is below 4 SD the peak bone mass at the spine and/or the hip.
The patient has a history of recent major upper gastrointestinal (GI) (esophagus, stomach, duodenum) mucosal erosive disease.
As defined by (1) significant upper GI bleeding within the last year resulting in hospitalization and/or transfusion. (2)
Recurrent ulcer disease documented by radiographic or endoscopic means (two episodes in the last two years, or any documented
ulcer in the preceeding 3 months). (3) Uncontrolled dyspepsia currently treated on a daily basis. (4) Esophageal or gastric
variceal disease or (5) esophageal stricture, achalasia, or severe esophageal motor dysfunction. (This only applies to Group
C and D)
The patient has a history of cancer with the following exceptions: (1) superficial basal or squamous cell carcinoma of the
skin that was treated, and (2) other malignancies treated at least 10 years ago without any evidence of recurrence.
The patient has a history of, or evidence for, metabolic bone disease (other than low bone mineral density) including, but
not limited to uncontrolled hyper- or hypocalcemia, hyper- or hypoparathyroidism, Paget's disease of bone, osteomalacia, or
osteogenesis imperfecta. Patients with surgically cured hyperparathyrodism due to parathyroid adenoma (at least one year
prior to randomization) are eligible for inclusion in the trial. Patients with well-controlled hyper- or hypothyrodism, as
indicated by clinical evaluation and normal plasma TSH level are eligible for inclusion in the trial.
The patient has received treatment prior to enrollment in the study that might have influenced bone turnover including:
Beginning a regimen (for more than 2 consecutive weeks) within the last 6 months, of any estrogen preparation including mixed
estrogen agonist/antagonist, (e.g., tamoxifen or raloxifene) or progestins.
Having used within the last 6 months any of the following: anabolic steroids (including DHEA and other weaker analogs), calcitonin,
calcitriol, alfacalcidol, excess vitamin A (greater than 10,000 units/day) or vitamin D (greater than 1,000 units/day), cyclosporine,
or anticonvulsivants.
The patient is on a thyroid hormone for treatment of a thyroid condition, unless the patient has received a stable dose for
the last 6 weeks prior to study enrollment, and is euthyroid, as documented by an ultrasensitive TSH serum assay.
The patient is on fluoride at a dose greater than 1 mg/day any time (fluoride taken greater than 3 months ago for less than
1 week is acceptable).
The patient has a history of glucocorticoid treatment for more than 1 month, within 6 months prior to study start (patients
who received therapeutic glucocorticoids in the past must be considered unlikely to need glucocorticoid treatment during the
course of the study).
Any previous treatment with bisphophonates for more than 2 weeks.
The patient's screening 25-hydroxyvitamin D level is less than 15 ng/mL unless 24-h urine calcium and serum PTH, calcium,
and alkaline phosphatase are all within the normal range.
The patient is not able to stand or sit upright for at least 30 minutes.
The patient has a body weight greater than 137 kg, due to limitations in the accuracy of DEXA measurements above this body
weight.
EXCLUSION CRITERIA RELATED TO THE EXERCISE (COOPER) TEST:
Subjects on beta-blockers will not be eligible to participate in the 12-min test.
INCLUSION CRITERIA - HEALTHY CONTROL WOMEN:
Healthy control women must be of good physical health; specifically, no history of any DSM-IV diagnoses, including but not
limited to depression and anorexia nervosa.
They also must have normal bone density, no history of osteoporotic fractures, and be willing to be on a valid contraceptive
method.
EXCLUSION CRITERIA - HEALTHY CONTROL WOMEN:
Control women should not have any of the risk factors for bone loss such as smoking, alcohol abuse, dietary imbalances unless
the risk factor is present only to a mild extent.
Location
and Contact
Information
Maryland National Institute of Mental Health (NIMH), 9000 Rockville Pike,
Bethesda,
Maryland,
20892,
United States; Recruiting
More Information
Detailed Web Page
Publications
Michelson D, Stratakis C, Hill L, Reynolds J, Galliven E, Chrousos G, Gold P. Bone mineral density in women with depression.
N Engl J Med. 1996 Oct 17;335(16):1176-81.
Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis.
JAMA. 1992 Mar 4;267(9):1244-52. Review.
Study ID Numbers:
000203; 00-M-0203
Record last reviewed:
July 13, 2003
Last Updated:
July 13, 2003
Record first received:
August 17, 2000
ClinicalTrials.gov Identifier:
NCT00006180Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08