Clinical trial NCT00043719: Nitroglycerin Ointment for Preventing Bone Loss in Postmenopausal Women
Official title: Prevention of Postmenopausal Bone Loss With Nitric Oxide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Osteopenia
Keywords: Human Female
Osteoporosis
Postmenopausal
Nitric Oxide
Nitroglycerin
Calcium
Vitamin D
Lead sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Sponsor class: NIH
First posted: 2002-08-14
Enrollment: 200
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Osteopenia and osteoporosis cause thinning of bone tissue and loss of bone density over time. The purpose of this study is to determine the safety and effectiveness of nitroglycerin ointment for the treatment of osteopenia in postmenopausal women.

Study hypothesis: On average, participants in the base therapy cohort who receive placebo ointment control and calcium/vitamin D will lose more bone density than participants in the nitroglycerin cohort over the 36-month period.

Detailed description: Imbalance in the activities of osteoclasts (cells responsible for bone loss) and osteoblasts (cells responsible for bone formation) may lead to fractures, osteopenia, and osteoporosis in postmenopausal women. During postmenopause, decreased estrogen levels and decreased nitric oxide production occur; estrogen replacement therapy has been shown to restore serum nitric oxide levels to normal. Reversing nitric oxide deficiency by using nitroglycerin may prevent further bone loss. The Nitroglycerin as an Option: Value in Early Bone Loss (NOVEL) study will test the safety and efficacy of nitroglycerin ointment for the treatment of osteopenia in postmenopausal women.

Patients will be enrolled in the study for 3 years and will be randomly assigned to one of two groups. The first group will receive nitroglycerin ointment, while the second group will receive placebo ointment. All patients will be given a calcium supplement with vitamin D to be taken daily, and will be instructed to rub the given ointment on their skin daily. Study visits will occur at Month 2 and every six months after Month 2. Phone interviews will be conducted with patients every 2 months throughout the study.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal for a minimum of 13 months
* Lumbar spine T-score of 0 to -2.5 (0 to -2.0 if over 60 years old) by Dual Energy X-ray Absorptiometry (DEXA) (i.e., evidence of normal bone mass or osteopenia)
* Body Mass Index (BMI) between 18 and 32
* Planning to live in the greater New Brunswick, NJ, area for at least 3 years

Exclusion Criteria:

* Radiographically or DEXA-morphometrically proven vertebral or hip fracture
* Conditions requiring routine use of sublingual, transdermal, or oral nitrates
* Significant postmenopausal symptoms that require estrogen therapy
* Metabolic bone diseases other than postmenopausal bone loss (e.g., active hyperthyroidism, hyperparathyroidism, Paget's disease of bone, etc.)
* Insulin-dependent diabetes mellitus
* Significant migraine headaches
* History of renal calculi
* Cancer within 5 years prior to study entry
* Any condition causing an anticipated life expectancy of less than 3 years
* Failure to maintain 75% to 125% compliance with open-label calcium with vitamin D regimen during the screening period

Primary outcomes:
measure: DXA-measured BMD (bone mineral density) of lumbar vertebrae (L2 to L4)
Secondary outcomes:
measure: DXA-measured BMD of dual hips (Ward's triangle, femoral neck, and trochanter)
measure: serum osteocalcin
measure: BS-ALP
measure: serum N-telopeptide
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: UMDNJ-Robert Wood Johnson Medical School, Department of Medicine, Division of Endocrinology
state: New Jersey
Study officials:
affiliation: UMDNJ - Robert Wood Johnson Medical School, Division of Endocrinology
name: Sunil J. Wimalawansa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: