Anorexia Nervosa
Conditions
Keywords
Adolescents, Anorexia nervosa (AN), Bone formation markers, Insulin like growth factor-1 (IGF-I)
Brief summary
The purpose of this study was to determine whether giving insulin like growth factor-I (IGF-I) to adolescent low weight girls is safe and whether this increases levels of bone formation markers.
Detailed description
Adolescents with anorexia nervosa (AN) are at high risk for low bone mineral density at a time when healthy adolescents are rapidly accruing bone, with implications for peak bone mass and fracture risk in later life. They are also deficient in insulin-like growth factor I (IGF-I), the bone trophic factor made in the liver in response to growth hormone (GH), despite elevated levels GH. It is possible that deficiency of IGF-I, a hormone very important for the maintenance of skeletal integrity, may contribute to the severe osteopenia seen in AN. The physiologic effects of rhIGF-I treatment in adolescents with AN had not been studied. The goal of this proposal was to investigate the acute effects of rhIGF-I on bone metabolism in adolescent girls with AN. Specific Aim: It was hypothesized that adolescent AN patients, being IGF-I deficient, would respond to exogenously administered rhIGF-I with elevations in biochemical indices of bone turnover. Therefore, rhIGF-I was administered to AN patients by subcutaneous injection over 10 days with concomitant measurement of indices of bone turnover, and calcium regulatory hormones.
Interventions
DRUGRhIGF-1
35-40 mcg/k/dose twice daily SC
Sponsors
Tercica
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Adolescent girls with anorexia nervosa 12-18 years old
Exclusion criteria
* Pregnancy or nursing * Hematocrit \< 30%, K \< 3 mmol/L * Any illness (other than anorexia nervosa) known to affect bone and mineral metabolism such as diabetes, alcoholism, untreated hypo- or hyperthyroidism, or hyperparathyroidism * History of use of any medicine, such as corticosteroids, known to affect bone density. Subjects who were on estrogen were still eligible to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Levels of Insulin Like Growth Factor-1 (IGF-I) Following Recombinant Human (rh) IGF-1 Administration in Girls With Anorexia Nervosa | Baseline and 7-10 days |
Secondary
| Measure | Time frame |
|---|---|
| Change in Levels of N-terminal Propeptide of Type 1 Procollagen (P1NP) Following rhIGF-1 Administration in Girls With Anorexia Nervosa | Baseline and 7-10 days |
Countries
United States
Participant flow
Recruitment details
Sixteen anorexia nervosa patients between the ages of 12-18 years were recruited. Patients were determined by their psychiatrists to meet criteria for AN as described in the Diagnostic and Statistical Manual of Mental Disorders (a).
Pre-assignment details
Four subjects were not interested in the study after the screen, and two were lost to follow-up.
Participants by arm
| Arm | Count |
|---|---|
| RhIGF-1 All study subjects were administered rhIGF-1 at a dose of 35-40 mcg/k/dose twice daily SC for 7-10 days. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | not interested in the study | 4 |
Baseline characteristics
| Characteristic | RhIGF-1 |
|---|---|
| Age, Categorical <=18 years | 16 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 16.2 years STANDARD_DEVIATION 0.5 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 16 |
| serious Total, serious adverse events | 1 / 16 |
Outcome results
Primary
Change in Levels of Insulin Like Growth Factor-1 (IGF-I) Following Recombinant Human (rh) IGF-1 Administration in Girls With Anorexia Nervosa
Time frame: Baseline and 7-10 days
Population: 16 subjects were screened for the study, and 10 completed the study. 10 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RhIGF-1 | Change in Levels of Insulin Like Growth Factor-1 (IGF-I) Following Recombinant Human (rh) IGF-1 Administration in Girls With Anorexia Nervosa | 542.9 ng/ml | Standard Error 40.9 |
Comparison: We used paired t-tests to assess changes in levels of IGF-1 from baseline levels in girls with AN receiving rhIGF-1. Our hypothesis was that rhIGF-1 administration would be associated with a significant increase in IGF-1 levels.p-value: <0.05Paired t-test
Secondary
Change in Levels of N-terminal Propeptide of Type 1 Procollagen (P1NP) Following rhIGF-1 Administration in Girls With Anorexia Nervosa
Time frame: Baseline and 7-10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RhIGF-1 | Change in Levels of N-terminal Propeptide of Type 1 Procollagen (P1NP) Following rhIGF-1 Administration in Girls With Anorexia Nervosa | 39.3 ng/ml | Standard Error 9.3 |
Comparison: We used a paired t-test to determine the change in P1NP from baseline to 7-10 days following administration of rhIGF-1p-value: <0.05Paired t-test