Type 1 DiabetesNCT00489645
Effect of Hyperglycemia on Gastric Emptying Interactions With Pramlintide
A study testing pramlintide in people with Type 1 Diabetes, run by Ludwig-Maximilians - University of Munich.
Trial summary
To examine the influence of acute glycaemia (normoglycaemia and hyperglycaemia) on gastric emptying kinetics in patients with type 1 diabetes and non diabetic subjects when treated with subcutaneous (SC) injections of pramlintide. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- pramlintide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- No sites listed yet
- Study dates
- Jan 2005to Apr 2007
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All of the following criteria are to be fulfilled for inclusion of an individual in the study unless the investigator grants an exception:
- Clinical diagnosis of type 1 diabetes (otherwise healthy) with an HbA1 ≤ 9%, and on a stable insulin treatment for at least 3 months (preferably on pump regimen) prior to screening OR is a healthy individual.
- 20-40 years of age, inclusive.
- Understand and sign an informed consent document, communicate with the investigator, and understand and comply with the requirements of the study.
- Euthyroid, including subjects receiving thyroid replacement therapy.
- If female:
Show all 12Show fewer
- Is surgically sterilized by hysterectomy; OR
- Is post-menopausal, as documented by a history of amenorrhea for 6 months and follicle stimulating hormone (FSH) level within the range specified as post-menopausal by the reporting laboratory at screen (post menopausal women on estrogen may enter the study without obtaining an FSH level); OR
- If of childbearing potential, meets the following criteria:
- negative pregnancy test (ß-HCG), regardless of birth control method (including subjects with tubal ligation);
- Practicing and willing to continue throughout the study the appropriate contraception (defined as oral, injected, or implanted contraceptives for at least 3 months prior to entry, or barrier contraception).
- Agree to take every precaution to ensure that pregnancy will not occur during the study.
Who cannot join
- Individuals meeting any of the following criteria are to be excluded from the study unless the investigator grants an exception:
- History of severe hypoglycemia.
- Body mass index (BMI) ≥ 30 kg/m2.
- Autonomic nerve dysfunction: abnormal result in the cardiovascular parasympathetic and/or sympathetic tests (screening visit).
- Hepatic disease:
- Known hepatic disease or transaminases (GOT, GPT) ≥ 2x above normal values.
Show all 35Show fewer
- Renal disease:
- Known or serum urea, serum creatinine ≥ 1.5x above normal values
- Cardiovascular or pulmonary disease:
- Arterial hypertension
- Blood pressure >150/95 mmHg at screening in a sitting position)
- Arterial occlusive disease
- Known coronary heart disease
- Abnormal ECG at screening visit.
- Gastrointestinal disease:
- Any known structural gastrointestinal disorder,
- Gastrointestinal surgery except for appendectomy,
- Symptoms indicating functional or structural upper gastrointestinal disorder (pain, bloating, postprandial fullness, nausea, emesis,
- Gastroectomy, gastroparesis, lactose intolerance, and diseases known to alter small bowel absorption; e.g., inflammatory bowel disease.
- CNS disease:
- Epilepsy (including subjects with a past history of convulsions associated with hypoglycaemia),
- Psychiatric illness (including history of eating disorder such as bulimia or anorexia).
- Autoimmune disease other than thyroid, pernicious anemia, or vitiligo.
- Malignant disease requiring chemotherapy,
- Any acute febrile illness within 2 weeks of Screening (Visit 1) with a temperature of 100°F,
- Currently abusing alcohol or drugs, or have a history of alcohol or drug abuse that in the investigator's opinion could cause the subject to be non-compliant; or have a general history of non-compliance with medications.
- Receipt of any investigational drug within 90 days of Screening (Visit 1) (prior treatment with pramlintide is permissible).
- Currently treated with medications known to interfere with gastric emptying such as, but not limited to:
- Ca2+ channel antagonists, ß-receptor antagonists, prokinetic agents metoclopramide (Reglan®) and cisapride (Propulsid®); and
- Chronic (more than 10 days within a 6-month period) macrolide antibiotics such as erythromycin and newer derivatives.
- Currently treated with:
- Bile acid sequestering resins cholestyramine (Questran®) and colestipol (Colestid®),
- Systemic steroids,
- Anti-obesity agents (including orlistat [Xenical®] and sibutramine [Meridia®]),
- Alpha-glucosidase inhibitors (acarbose [Precose®] and miglitol [Glyset®]) and meglitinides ([Prandin®] and [Starlix®]).
About this study
Official title: The Influence of Ambient Glycemia on the Effect of Pramlintide on Gastric Emptying in Patients With Type 1 Diabetes and Healthy Subjects
- To examine the influence of acute glycaemia (normoglycaemia and hyperglycaemia) on gastric emptying kinetics in patients with type 1 diabetes and non diabetic subjects when treated with subcutaneous (SC) injections of pramlintide.
Read the detailed description
Postprandial increases in plasma glucose concentrations are mainly determined by the degree of postprandial suppression of endogenous glucose production and the rate of appearance of the ingested glucose. The latter is predominantly determined by the amount of glucose taken up by the splanchnic bed. Because nutrient absorption depends on gastric nutrient delivery, gastric emptying rate is a key determinant of the early rise of plasma glucose postprandially. At mealtime, the faster the stomach empties the more rapid the rise in plasma glucose. Yet, plasma glucose concentration is a determinant of gastric emptying rate. In non-diabetic subjects, as plasma glucose rises and approaches the upper limit of the normal range (~140 mg/dl), gastric emptying slows. This likely represents a physiological brake mechanism to limit excess delivery of nutrients, thus avoiding excessive appearance of glucose in plasma. In diabetes, abnormally accelerated gastric emptying as well as delayed gastric emptying have been reported. These conflicting data may be explained by differences of ambient glycaemia. In most of these studies undertaken in diabetic subjects these patients were severely hyperglycaemic, thus the reported delayed gastric emptying may be explained by the effect of hyperglycaemia on gastric motility. Indeed, a small number of studies controlled for ambient glycaemia found acceleration of gastric emptying in diabetes and suggest that diabetes manifests with a maladaptive acceleration of gastric emptying likely contributing to excessive postprandial plasma glucose excursions.
The amylin analog pramlintide is a potential new therapeutic that elicits a potent glucose lowering effect in the postprandial period thought to be due to both a suppression of plasma glucagon and a delay of gastric emptying. It is not clear, however, to what extent the pramlintide-induced delay of gastric emptying offsets a potential maladaptive acceleration of gastric emptying in diabetes patients studied under controlled glycemic conditions. In theory, every drug that reduces hyperglycaemia should accelerate gastric emptying and, thereby, minimize its potential effect on postprandial hyperglycaemia. Thus, the drug-induced effect of amylin on gastric motility may be of great advantage by offset the effects of glycemic induced acceleration on gastric emptying.
- Conditions
- Type 1 Diabetes
- Being tested
- placebo, pramlintide
- Keywords
- pramlintide, gastric emptying, T1DM, postprandial
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboDrug
placebo SC during euglycemia
pramlintideDrug
pramlintide SC during eglycemia
placeboDrug
placebo during hyperglycemia
pramlintideDrug
pramlintide SC during hyperglycemia
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Placebo, euglycemia Receives: Drug: placebo |
| 2 | Experimental | Pramlintide, euglycemia Receives: Drug: pramlintide |
| 3 | Placebo comparator | placebo, hyperglycemia Receives: Drug: placebo |
| 4 | Experimental | pramlintide, hyperglycemia Receives: Drug: pramlintide |
What is being measured
The primary outcome is the main question the study is designed to answer.
• To examine the influence of acute glycaemia (normoglycaemia and hyperglycaemia) on gastric emptying kinetics in patients with type 1 diabetes and non diabetic subjects when treated with subcutaneous (SC) injections of pramlintide.
Measured: 2 years
Secondary outcomes (1)
• Gastric peristalsis derived from high-resolution scintigraphy by means of Fast Fourier Transform (FFT) analysis. • Effects on gastric emptying and on the rate of appearance of ingested glucose appearance, postprandial glucose sequestration, endoge
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2007 (estimated)
- Study startJan 2005
- Primary completionMar 2007
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- University of Rochester
- Investigators
- Joerg Schirra, MD, Principal investigator, Ludwig-Maximilians-University of Munic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00489645
- Sponsor's protocol ID
- PRAM025/04
- Other IDs
- DFG Schi 527/1-2
- Status last verified
- Jan 2008
- First submitted
- 19 Jun 2007
- Last updated
- 16 Jan 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Ambient Glycemia on the Effect of Pramlintide on Gastric Emptying in Patients With Type 1 Diabetes and Healthy Subjects
- ClinicalTrials.gov ID
- NCT00489645
- Acronym / sponsor ID
- PRAM025/04
- Conditions
- Type 1 Diabetes
- Keywords
- pramlintide, gastric emptying, T1DM, postprandial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Collaborators
- University of Rochester
- Study start
- Jan 2005
- Primary completion
- Mar 2007 (actual)
- Study completion
- Apr 2007 (actual)
- First posted
- 21 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- To examine the influence of acute glycaemia (normoglycaemia and hyperglycaemia) on gastric emptying kinetics in patients with type 1 diabetes and non diabetic subjects when treated with subcutaneous (SC) injections of pramlintide.
Detailed description
Postprandial increases in plasma glucose concentrations are mainly determined by the degree of postprandial suppression of endogenous glucose production and the rate of appearance of the ingested glucose. The latter is predominantly determined by the amount of glucose taken up by the splanchnic bed. Because nutrient absorption depends on gastric nutrient delivery, gastric emptying rate is a key determinant of the early rise of plasma glucose postprandially. At mealtime, the faster the stomach empties the more rapid the rise in plasma glucose. Yet, plasma glucose concentration is a determinant of gastric emptying rate. In non-diabetic subjects, as plasma glucose rises and approaches the upper limit of the normal range (~140 mg/dl), gastric emptying slows. This likely represents a physiological brake mechanism to limit excess delivery of nutrients, thus avoiding excessive appearance of glucose in plasma. In diabetes, abnormally accelerated gastric emptying as well as delayed gastric emptying have been reported. These conflicting data may be explained by differences of ambient glycaemia. In most of these studies undertaken in diabetic subjects these patients were severely hyperglycaemic, thus the reported delayed gastric emptying may be explained by the effect of hyperglycaemia on gastric motility. Indeed, a small number of studies controlled for ambient glycaemia found acceleration of gastric emptying in diabetes and suggest that diabetes manifests with a maladaptive acceleration of gastric emptying likely contributing to excessive postprandial plasma glucose excursions.
The amylin analog pramlintide is a potential new therapeutic that elicits a potent glucose lowering effect in the postprandial period thought to be due to both a suppression of plasma glucagon and a delay of gastric emptying. It is not clear, however, to what extent the pramlintide-induced delay of gastric emptying offsets a potential maladaptive acceleration of gastric emptying in diabetes patients studied under controlled glycemic conditions. In theory, every drug that reduces hyperglycaemia should accelerate gastric emptying and, thereby, minimize its potential effect on postprandial hyperglycaemia. Thus, the drug-induced effect of amylin on gastric motility may be of great advantage by offset the effects of glycemic induced acceleration on gastric emptying.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: placeboPlacebo, euglycemia |
| 2 | Experimental | Drug: pramlintidePramlintide, euglycemia |
| 3 | Placebo comparator | Drug: placeboplacebo, hyperglycemia |
| 4 | Experimental | Drug: pramlintidepramlintide, hyperglycemia |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- All of the following criteria are to be fulfilled for inclusion of an individual in the study unless the investigator grants an exception:
- Clinical diagnosis of type 1 diabetes (otherwise healthy) with an HbA1 ≤ 9%, and on a stable insulin treatment for at least 3 months (preferably on pump regimen) prior to screening OR is a healthy individual.
- 20-40 years of age, inclusive.
- Understand and sign an informed consent document, communicate with the investigator, and understand and comply with the requirements of the study.
- Euthyroid, including subjects receiving thyroid replacement therapy.
Key exclusion criteria (35 listed)
- Individuals meeting any of the following criteria are to be excluded from the study unless the investigator grants an exception:
- History of severe hypoglycemia.
- Body mass index (BMI) ≥ 30 kg/m2.
- Autonomic nerve dysfunction: abnormal result in the cardiovascular parasympathetic and/or sympathetic tests (screening visit).
- Known hepatic disease or transaminases (GOT, GPT) ≥ 2x above normal values.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboplacebo SC during euglycemia | Drug | 1 |
| pramlintidepramlintide SC during eglycemia | Drug | 2 |
| placeboplacebo during hyperglycemia | Drug | 3 |
| pramlintidepramlintide SC during hyperglycemia | Drug | 4 |
Primary outcome
• To examine the influence of acute glycaemia (normoglycaemia and hyperglycaemia) on gastric emptying kinetics in patients with type 1 diabetes and non diabetic subjects when treated with subcutaneous (SC) injections of pramlintide.
Time frame: 2 years
1 secondary outcome
• Gastric peristalsis derived from high-resolution scintigraphy by means of Fast Fourier Transform (FFT) analysis. • Effects on gastric emptying and on the rate of appearance of ingested glucose appearance, postprandial glucose sequestration, endoge
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2008.
Related trials for Type 1 Diabetes
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joerg Schirra, MD principal investigator
Ludwig-Maximilians-University of Munic
Questions about this trial
What is this clinical trial studying?
A study testing pramlintide in people with Type 1 Diabetes, run by Ludwig-Maximilians - University of Munich.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2008. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• To examine the influence of acute glycaemia (normoglycaemia and hyperglycaemia) on gastric emptying kinetics in patients with type 1 diabetes and non diabetic subjects when treated with subcutaneous (SC) injections of pramlintide. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2008.