Bone Loss in Premenopausal Women With Depression

NCT00006180 | Completed Phase 4

• 2 other identifiers: 00020300-M-0203
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depression; Healthy; Osteopenia; Osteoporosis

Keywords

Preventive Medicine; Women's Health; Bone Formation; Mood Disorders; Bone Resorption; Major Depression; Osteopenia; Osteoporosis; Bone Fracture; Bisphosphonate; Depression; Bone Density; Healthy Volunteer; HV; Normal Control

Interventions

Alendronate DRUG

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• The patient had 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 1538563 BACKGROUND

• Cizza G, Mistry S, Nguyen VT, Eskandari F, Martinez P, Torvik S, Reynolds JC, Gold PW, Sinaii N, Csako G; POWER Study Group. Do premenopausal women with major depression have low bone mineral density? A 36-month prospective study. PLoS One. 2012;7(7):e40894. doi: 10.1371/journal.pone.0040894. Epub 2012 Jul 27.

  PMID: 22848407 DERIVED

• Cizza G, Ronsaville DS, Kleitz H, Eskandari F, Mistry S, Torvik S, Sonbolian N, Reynolds JC, Blackman MR, Gold PW, Martinez PE; P.O.W.E.R. (Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression) Study Group. Clinical subtypes of depression are associated with specific metabolic parameters and circadian endocrine profiles in women: the power study. PLoS One. 2012;7(1):e28912. doi: 10.1371/journal.pone.0028912. Epub 2012 Jan 3.

  PMID: 22235252 DERIVED

• Eskandari F, Martinez PE, Torvik S, Phillips TM, Sternberg EM, Mistry S, Ronsaville D, Wesley R, Toomey C, Sebring NG, Reynolds JC, Blackman MR, Calis KA, Gold PW, Cizza G; Premenopausal, Osteoporosis Women, Alendronate, Depression (POWER) Study Group. Low bone mass in premenopausal women with depression. Arch Intern Med. 2007 Nov 26;167(21):2329-36. doi: 10.1001/archinte.167.21.2329.

  PMID: 18039992 DERIVED

MeSH Terms

Conditions

Depression; Bone Diseases, Metabolic; Osteoporosis; Mood Disorders; Bone Resorption; Depressive Disorder, Major; Fractures, Bone

Interventions

Alendronate

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Mental Disorders; Depressive Disorder; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: August 17, 2000
• First Posted: August 18, 2000
• Study Start: August 10, 2000
• Study Completion: January 19, 2007
• Last Updated: July 2, 2017

Record last verified: 2007-01-19

Locations

US (1)