Osteoporosis
Conditions
Keywords
Gastric acid, Dietary protein, Calcium, Intestinal absorption, Calcium sensing receptor
Brief summary
We have established that dietary protein is an important regulator of intestinal calcium absorption in humans. However, we do not understand the mechanism by which dietary protein is affecting calcium absorption. Therefore, the purpose of this research is to evaluate whether dietary protein-induced changes in gastric acid secretion explain the observed changes in intestinal calcium absorption.
Detailed description
We have established that dietary protein is an important regulator of intestinal calcium absorption in humans. However, we do not understand the mechanism by which dietary protein is affecting calcium absorption. Therefore, the purpose of this research is to evaluate whether dietary protein-induced changes in gastric acid secretion explain the observed changes in intestinal calcium absorption. We have compelling in vitro data that amino acids can stimulate gastric acid secretion. We have found that this occurs via allosteric activation of the calcium sensing receptor expressed on the gastric acid-secreting parietal cells. At a fixed concentration of extracellular calcium, addition of L but not D isomers of specific amino acids activates the calcium sensing receptor and stimulates parietal cell acid production. We hypothesize that dietary protein induced gastric acid production increases calcium solubility and bioavailability thereby increasing its absorption. We will test this hypothesis in humans by quantifying the impact of dietary protein on intestinal calcium absorption in subjects who cannot make gastric acid. We will measure intestinal calcium absorption in healthy adults as they consume either a high protein diet with concomitant administration of a proton pump inhibiting (PPI) drug or the same high protein diet with a placebo instead of a PPI. The order of the 2 interventions will be randomized, and study will be double-blind and placebo controlled. If our hypothesis is correct, then intestinal calcium absorption will be highest during the high protein diet with placebo, and lowest during the drug intervention.
Interventions
DRUGesomeprazole
2 Interventions with esomeprazole 20 mg twice a day for 9 days vs. a placebo for 9 days while on a high protein diet
DRUGPlacebo
Placebo 20 mg twice a day for 9 days
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and women age 18-45 years * Caucasian or Asian descent due to increased risk of Osteoporosis
Exclusion criteria
* gastrointestinal diseases * osteoporosis * diabetes * hypertension * liver disease * thyroid disorders * kidney disease * kidney stones * cancer * heart disease * eating disorders * obesity * hypogonadism * amenorrhea * oligomenorrhea * abnormal serum FSH or estradiol levels * birth control medication or other hormone-altering medications * pregnancy * Lifestyle factors such as: * smoking * excessive exercise (although moderate exercise is allowed) * prescription medications known to influence vitamin D or calcium metabolism or gastric acid * excessive body weight change during the past 6 months * food allergies * unusual eating habits or medically prescribed diets
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Intestinal Calcium Absorption | Day 5 of a high protein diet | This is completed by measuring the amount of calcium absorbed by utilizing dual stable calcium isotopes. It was hypothesized that we would see a percent decrease as a result of the proton pump inhibitor. Previous published data indicated a decline in calcium absorption of 6.6 +/- 5.5% when gastric pH is blocked. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastric pH | Day 5 of a high protein diet | The American Heritage Dictionary defines pH as a measure of the acidity or alkalinity of a solution, numerically equal to 7 for neutral solutions, increasing with increasing alkalinity and decreasing with increasing acidity. The pH scale commonly in use ranges from 0 to 14. The normal pH range for stomach acid is between 1.5 and 3.5. |
Countries
United States
Participant flow
Recruitment details
12 healthy women and men enrolled
Pre-assignment details
Participants received either Esomeprazole or placebo first and then crossed over to receive the other intervention with a minimum 2 week washout in-between.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive 20 mg twice daily of either placebo or esomeprazole first | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 30.9 years STANDARD_DEVIATION 8.3 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Percent Change in Intestinal Calcium Absorption
This is completed by measuring the amount of calcium absorbed by utilizing dual stable calcium isotopes. It was hypothesized that we would see a percent decrease as a result of the proton pump inhibitor. Previous published data indicated a decline in calcium absorption of 6.6 +/- 5.5% when gastric pH is blocked.
Time frame: Day 5 of a high protein diet
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole | Percent Change in Intestinal Calcium Absorption | 34.2 percentage of calcium absorption | Standard Error 2.4 |
| Placebo | Percent Change in Intestinal Calcium Absorption | 31.5 percentage of calcium absorption | Standard Error 2.1 |
Secondary
Gastric pH
The American Heritage Dictionary defines pH as a measure of the acidity or alkalinity of a solution, numerically equal to 7 for neutral solutions, increasing with increasing alkalinity and decreasing with increasing acidity. The pH scale commonly in use ranges from 0 to 14. The normal pH range for stomach acid is between 1.5 and 3.5.
Time frame: Day 5 of a high protein diet
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole | Gastric pH | 5.38 units on a scale of pH | Standard Error 0.13 |
| Placebo | Gastric pH | 2.70 units on a scale of pH | Standard Error 0.44 |