Hyperinsulinemic HypoglycemiaPhase 1NCT03103009
Treatment Plan for an Individual Patient With Pasireotide for Hyperinsulinemic Hypoglycemia
A Phase 1 study testing Pasireotide in people with Hyperinsulinemic Hypoglycemia and Post Gastrointestinal Tract Surgery Hypoglycaemia, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Somatostatin analogues are a last resort for medical intervention in hyperinsulinemic hypoglycemia (HH). The hypoglycemia is very debilitating and can be even life threatening. There is limited experience with pasireotide in hyperinsulinemic hypoglycemia (only one publication); there is more experience with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperinsulinemic Hypoglycemia, Post Gastrointestinal Tract Surgery Hypoglycaemia
- What is being tested?
- Pasireotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Mar 2017to 22 Dec 2017
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients eligible for inclusion in this Treatment Plan have to meet all of the following criteria:
- Male or female patients aged 18 years or older
- Patients with a confirmed diagnosis of hyperinsulinemic hypoglycemia, if possible by genetic testing
- Patients not controlled by medical therapies (e.g. diazoxide or octreotide) and/or pancreatic surgery or patients not eligible for surgery
- WHO/ ECOG Performance Status of 0-2.
- Life expectancy ≥12 weeks
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- Adequate end organ function as defined by:
- No evidence of significant liver disease:
- Serum total bilirubin ≤1.5 x ULN
- INR < 1.3
- ALT and AST ≤ 2 x ULN,
- Alkaline phosphatase ≤ 2.5 x ULN
- Written informed consent obtained prior to treatment to be consistent with local regulatory requirements
- Is suffering from a serious or life-threatening disease or condition
- Does not have access to a comparable or satisfactory alternative treatment (i.e., comparable or satisfactory treatment is not available or does not exist)
- Is not eligible for participation in any of the IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient
- There are meaningful human clinical data to support an assessment that the potential benefits to patient outweigh risks.
- Meets any other relevant medical criteria for compassionate use of the investigational product
- Is not being transferred from an ongoing clinical trial for which they are still eligible
Who cannot join
- Patients eligible for this Treatment Plan must not meet any of the following criteria:
- Patients with a known hypersensitivity to somatostatin analogs or any component of the pasireotide LAR or s.c. formulations.
- Patients with abnormal coagulation (PT or aPTT elevated by 30% above normal limits).
- Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.
- Patients currently using warfarin / warfarin derivatives
- Patients with symptomatic cholelithiasis.
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- Patients who are not biochemically euthyroid. Patients with known history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months.
- QT-related exclusion criteria: :
- QTcF at screening > 450 msec in males and QTcF > 460 msec
- History of syncope or family history of idiopathic sudden death
- Sustained or clinically significant cardiac arrhythmias
- Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block
- Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
- Family history of long QT syndrome
- Concomitant medications known to prolong the QT interval.
- Potassium < or = 3.5 mmol/L
- Patients who have any severe and/or uncontrolled medical conditions :
- Uncontrolled diabetes as defined by HbA1c > 8%,
- Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, including a positive HIV test result (ELISA and Western blot). An HIV test will not be required; however, previous medical history will be reviewed.
- Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment.
- Life-threatening autoimmune and ischemic disorders.
- Patients who have a history of another primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix. Patients who have had no evidence of disease from another primary cancer for 1 or more years are allowed to participate in the study.
- Patients with history of liver disease, such as cirrhosis or chronic active hepatitis B or C
- Presence of Hepatitis B surface antigen (HbsAg)
- Presence of Hepatitis C antibody (anti-HCV)
- History of, or current alcohol misuse/abuse within the past 12 months.
- Known gallbladder or bile duct disease, acute or chronic pancreatitis
- Patients with hypomagnesaemia (< 0.7 mmol/L)
- Patients with a history of non-compliance to medical regimens or who are considered potentially
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing. Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
- Combination of any two of the following (a+b or a+c, or b+c):
- Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
- If the patient is a sexually active male he is excluded unless he agrees to use a condom during intercourse while taking pasireotide and for 3 months after stopping pasireotide medication . They should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Somatostatin analogues are a last resort for medical intervention in hyperinsulinemic hypoglycemia (HH). The hypoglycemia is very debilitating and can be even life threatening. There is limited experience with pasireotide in hyperinsulinemic hypoglycemia (only one publication); there is more experience with octreotide, both in adults and children successful interventions with octreotide in hyperinsulinemic hypoglycemia have been published. Pasireotide via its different somatostatin receptor binding profile has clear effects on insulin, glucagon and incretin secretion and can ultimately lead to hyperglycemia. This mode of action (especially the effects on insulin and incretin secretion) could be very useful in the setting of hyperinsulinemic hypoglycemia.
Read the detailed description
Hyperinsulinemic hypoglycemia as a complication of gastric bypass surgery has been reported to occur between 6 months to 8-10 years after gastric bypass surgery. Although reported as a rare complication from surgery, the incidence is likely higher due to the condition being missed in many patients or being misdiagnosed as dumping syndrome. Unlike dumping syndrome which often presents early in the post-operative course and improves with dietary modification, patients with hyperinsulinemic hypoglycemia have severe postprandial hypoglycemia and sometimes fasting hypoglycemia with symptoms worsening over time despite dietary modification. Calcium stimulation testing often localizes the area of the pancreas where hyperinsulinemia is occurring due to islet cell dysfunction. The pathophysiology of islet cell hypertrophy with Nesidioblastosis is poorly understood. One theory is an increase in glucagon-like peptide-1 (GLP-1) concentration may be responsible for islet cell expansion and subsequent hyperinsulinemic hypoglycemia.
Unfortunately, hyperinsulinemia hypoglycemia is incapacitating where patients are restricted from driving, are unable to work, and must always have someone present with glucagon due to the acute severe onset of neuroglycopenia. Surgery to resect the area of the pancreas with Nesidioblastosis has a low success rate of about 60% with many patients developing type 1 diabetes as a result of pancreatic resection. Medical treatment options include calcium channel blockers, Diazoxide, and Octreotide yet patients often fail these treatments as well. Pasireotide would likely be a better option than the current medical therapy available. With Pasireotide, the inhibition of insulin release through inhibiting the somatostatin receptors as well as possible GLP-1 inhibition causing hyperglycemia should reduce hypoglycemic episodes in these patients.
- Being tested
- Pasireotide
- Medical subject headings
- Congenital Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PasireotideDrug
Also called Signifor
Somatostatin analogues are a last resort for medical intervention in hyperinsulinemic hypoglycemia (HH). The hypoglycemia is very debilitating and can be even life threatening. There is limited experience with pasireotide in hyperinsulinemic hypoglycemia (only one publication); there is more experience with octreotide, both in adults and children and successful interventions with octreotide in hyperinsulinemic hypoglycemia have been published. Pasireotide via its different somatostatin receptor binding profile has clear effects on insulin, glucagon and incretin secretion and can ultimately lead to hyperglycemia. This mode of action (especially the effects on insulin and incretin secretion) could be very useful in the setting of hyperinsulinemic hypoglycemia.
| Study group | Role | What they receive |
|---|---|---|
| pasireotide | Experimental | Interventions - One patient will be given a drug, pasireotide (Signifor), on a compassionate use basis for treatment of post-gastric bypass hypoglycemia. The minimal dose will be 0.3 mg subcutaneous daily and the maximal dose will be 0.6 mg subcutaneous twice daily. The patient may continue treatment with pasireotide indefinitely unless the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued at the discretion of the treating physician or Novartis or withdrawal of consent. Receives: Drug: Pasireotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recording of Hypoglycemic events
The primary outcome is the number of hypoglycemic events occurring.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2017
- Study start22 Mar 2017
- Primary completion22 Dec 2017
- Study completion22 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyperinsulinemic HypoglycemiaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Treatment Plan for an individual patient with pasireotide for Hyperinsulinemic Hypoglycemia (Compassionate Use Protocol for Pasireotide)
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Helen Lawler, MD, Principal investigator, University of Colorado, DenverMike McDermott, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03103009
- Sponsor's protocol ID
- 16-0393
- Status last verified
- Sep 2021
- First submitted
- 31 Mar 2017
- Last updated
- 29 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared with Novartis.
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Plan for an Individual Patient With Pasireotide for Hyperinsulinemic Hypoglycemia
- ClinicalTrials.gov ID
- NCT03103009
- Acronym / sponsor ID
- 16-0393
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 22 Mar 2017 (actual)
- Primary completion
- 22 Dec 2017 (actual)
- Study completion
- 22 Dec 2017 (actual)
- First posted
- 6 Apr 2017 (actual)
- 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.
Somatostatin analogues are a last resort for medical intervention in hyperinsulinemic hypoglycemia (HH). The hypoglycemia is very debilitating and can be even life threatening. There is limited experience with pasireotide in hyperinsulinemic hypoglycemia (only one publication); there is more experience with octreotide, both in adults and children successful interventions with octreotide in hyperinsulinemic hypoglycemia have been published. Pasireotide via its different somatostatin receptor binding profile has clear effects on insulin, glucagon and incretin secretion and can ultimately lead to hyperglycemia. This mode of action (especially the effects on insulin and incretin secretion) could be very useful in the setting of hyperinsulinemic hypoglycemia.
Detailed description
Hyperinsulinemic hypoglycemia as a complication of gastric bypass surgery has been reported to occur between 6 months to 8-10 years after gastric bypass surgery. Although reported as a rare complication from surgery, the incidence is likely higher due to the condition being missed in many patients or being misdiagnosed as dumping syndrome. Unlike dumping syndrome which often presents early in the post-operative course and improves with dietary modification, patients with hyperinsulinemic hypoglycemia have severe postprandial hypoglycemia and sometimes fasting hypoglycemia with symptoms worsening over time despite dietary modification. Calcium stimulation testing often localizes the area of the pancreas where hyperinsulinemia is occurring due to islet cell dysfunction. The pathophysiology of islet cell hypertrophy with Nesidioblastosis is poorly understood. One theory is an increase in glucagon-like peptide-1 (GLP-1) concentration may be responsible for islet cell expansion and subsequent hyperinsulinemic hypoglycemia.
Unfortunately, hyperinsulinemia hypoglycemia is incapacitating where patients are restricted from driving, are unable to work, and must always have someone present with glucagon due to the acute severe onset of neuroglycopenia. Surgery to resect the area of the pancreas with Nesidioblastosis has a low success rate of about 60% with many patients developing type 1 diabetes as a result of pancreatic resection. Medical treatment options include calcium channel blockers, Diazoxide, and Octreotide yet patients often fail these treatments as well. Pasireotide would likely be a better option than the current medical therapy available. With Pasireotide, the inhibition of insulin release through inhibiting the somatostatin receptors as well as possible GLP-1 inhibition causing hyperglycemia should reduce hypoglycemic episodes in these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Treatment Plan for an individual patient with pasireotide for Hyperinsulinemic Hypoglycemia (Compassionate Use Protocol for Pasireotide)
| Arm | Type | Receives |
|---|---|---|
| pasireotide | Experimental | Drug: PasireotideInterventions - One patient will be given a drug, pasireotide (Signifor), on a compassionate use basis for treatment of post-gastric bypass hypoglycemia. The minimal dose will be 0.3 mg subcutaneous daily and the maximal dose will be 0.6 mg subcutaneous twice daily. The patient may continue treatment with pasireotide indefinitely unless the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued at the discretion of the treating physician or Novartis or withdrawal of consent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients eligible for inclusion in this Treatment Plan have to meet all of the following criteria:
- Male or female patients aged 18 years or older
- Patients with a confirmed diagnosis of hyperinsulinemic hypoglycemia, if possible by genetic testing
- Patients not controlled by medical therapies (e.g. diazoxide or octreotide) and/or pancreatic surgery or patients not eligible for surgery
- WHO/ ECOG Performance Status of 0-2.
Key exclusion criteria (39 listed)
- Patients with a known hypersensitivity to somatostatin analogs or any component of the pasireotide LAR or s.c. formulations.
- Patients with abnormal coagulation (PT or aPTT elevated by 30% above normal limits).
- Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.
- Patients currently using warfarin / warfarin derivatives
- Patients with symptomatic cholelithiasis.
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 |
|---|---|---|
| PasireotideAlso: SigniforSomatostatin analogues are a last resort for medical intervention in hyperinsulinemic hypoglycemia (HH). The hypoglycemia is very debilitating and can be even life threatening. There is limited experience with pasireotide in hyperinsulinemic hypoglycemia (only one publication); there is more experience with octreotide, both in adults and children and successful interventions with octreotide in hyperinsulinemic hypoglycemia have been published. Pasireotide via its different somatostatin receptor binding profile has clear effects on insulin, glucagon and incretin secretion and can ultimately lead to hyperglycemia. This mode of action (especially the effects on insulin and incretin secretion) could be very useful in the setting of hyperinsulinemic hypoglycemia. | Drug | pasireotide |
Primary outcome
Recording of Hypoglycemic events
Time frame: Up to 2 years
The primary outcome is the number of hypoglycemic events occurring.
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 29 Sep 2021.
- Individual participant dataSharing planned: Yes. Data will be shared with Novartis.
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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.
Helen Lawler, MD principal investigator
University of Colorado, Denver
Mike McDermott, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pasireotide in people with Hyperinsulinemic Hypoglycemia and Post Gastrointestinal Tract Surgery Hypoglycaemia, run by University of Colorado, Denver at 1 site in United States.
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 19 inclusion and 39 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 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Recording of Hypoglycemic events (time frame: Up to 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 29 Sep 2021.