Fasting
Conditions
Keywords
leptin, fasting, reproductive, neuroendocrine, immune function, energy deficiency associated with short-term fasting
Brief summary
The purpose of this study will be to determine whether giving leptin (r-metHuLeptin) to a person when he or she is fasting will reverse changes in metabolism, and hormone levels, and immune function associated with fasting, which decreases leptin levels.
Detailed description
Leptin is a hormone secreted by fat cells under normal conditions and acts in the brain to decrease appetite and increase energy use. Leptin levels usually go down with fasting. This study will evaluate the secretion of an investigational agent called leptin in lean and overweight individuals while fasting and investigate the potential role of leptin as a regulator of immune function and mediator of the neuroendocrine response to food deprivation in humans. Data derived from these studies will provide insights into the mechanisms underlying altered hormone levels and immune function in malnutrition and obesity and thus may provide the basis for future therapeutic interventions for obesity. Comparison: fed state vs. fasting state vs. fasting + leptin state
Interventions
DRUGr-metHuLeptin
recombinant human leptin
OTHERplacebo
placebo (no active drug)
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Research Resources (NCRR)
Amgen
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy lean women (with body mass indices \[BMI\] \< 25 kg/m2) * Overweight otherwise healthy men (with BMI \> 27 kg/m2) * Overweight otherwise healthy women (with BMI \> 27 kg/m2).
Exclusion criteria
* A history of any illness that may affect the concentrations of the hormones to be studied, e.g. infectious diseases, renal or hepatic failure, type 1 or type 2 diabetes mellitus, cancer or lymphoma, hypogonadism, malabsorption or malnourishment, hypo- or hyperthyroidism, hypercortisolism, alcoholism or drug abuse, anemia, or eating disorder * On medications known to affect the hormones to be measured (glucocorticoids, anti-seizure medications, and thyroid hormones) * A known history of anaphylaxis or anaphylactoid-like reactions, or a known hypersensitivity to E. coli derived proteins
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cortisol | four days | — |
| ACTH Mean Level | 4 days | Response of ACTH to leptin administration in fed and fasting state from baseline was measured |
| Immune Function CD3 Count | 4 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| %Fat Mass | four days | — |
| (RMR) | four days | Resting Metabolic rate using calorimetry |
| Autonomic Function | four days | aldosterone level were measured on day 4 in response to leptin in fed and fasting states and compared with baseline level on day 1 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iso Fed, Then Fasting w/ Metreleptin, Then Fasting w/ Placebo r-metHuLeptin self-administered subcutaneously
r-metHuLeptin: recombinant human leptin | 7 |
| Iso Fed, Then Fasting w/ Placebo, Then Fasting w/ Metreleptin Placebo, administered in same method as active arm.
placebo: placebo (no active drug) | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | Iso Fed, Then Fasting w/ Placebo, Then Fasting w/ Metreleptin | Iso Fed, Then Fasting w/ Metreleptin, Then Fasting w/ Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Continuous | 25 years STANDARD_DEVIATION 5 | 26 years STANDARD_DEVIATION 5 | 25.5 years STANDARD_DEVIATION 0.5 |
| Region of Enrollment United States | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
ACTH Mean Level
Response of ACTH to leptin administration in fed and fasting state from baseline was measured
Time frame: 4 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metreleptin | ACTH Mean Level | fasting | 9.89 pg/ml | Standard Error 2.01 |
| Metreleptin | ACTH Mean Level | baseline fed | 10.48 pg/ml | Standard Error 1.28 |
| Placebo | ACTH Mean Level | baseline fed | 9.33 pg/ml | Standard Error 1.23 |
| Placebo | ACTH Mean Level | fasting | 8.74 pg/ml | Standard Error 1.75 |
Primary
Cortisol
Time frame: four days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metreleptin | Cortisol | 17.5 ug/dl | Standard Deviation 0.9 |
| Placebo | Cortisol | 16.9 ug/dl | Standard Deviation 1.9 |
Primary
Immune Function CD3 Count
Time frame: 4 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metreleptin | Immune Function CD3 Count | 302 cells/ul | Standard Error 185 |
| Placebo | Immune Function CD3 Count | 838 cells/ul | Standard Error 268 |
Secondary
Autonomic Function
aldosterone level were measured on day 4 in response to leptin in fed and fasting states and compared with baseline level on day 1
Time frame: four days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metreleptin | Autonomic Function | Day 4 | 132 pg/ml | Standard Error 27 |
| Metreleptin | Autonomic Function | day 1 baseline | 66.1 pg/ml | Standard Error 11.7 |
| Placebo | Autonomic Function | Day 4 | 112 pg/ml | Standard Error 23.5 |
| Placebo | Autonomic Function | day 1 baseline | 66.0 pg/ml | Standard Error 12.8 |
Secondary
%Fat Mass
Time frame: four days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metreleptin | %Fat Mass | 29.1 fat% | Standard Deviation 2.2 |
| Placebo | %Fat Mass | 29.3 fat% | Standard Deviation 1.9 |
Secondary
(RMR)
Resting Metabolic rate using calorimetry
Time frame: four days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metreleptin | (RMR) | 1.344 kcal/d | Standard Deviation 34 |
| Placebo | (RMR) | 1.352 kcal/d | Standard Deviation 43 |