Severe Insulin ResistancePhase 2NCT00085982
Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance
A Phase 2 study testing Metreleptin in people with Severe Insulin Resistance, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Study Description: Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Severe Insulin Resistance
- What is being tested?
- Metreleptin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Aug 2003to 1 Jan 2030
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Male or female, aged > 5 years
- Clinically significant, severe insulin resistance caused by a known or suspected defect in the insulin receptor
- Presence of at least one of the following metabolic abnormalities:
- Fasting insulin >30 micro U/ml, or
- Presence of diabetes as defined by the 2006 American Diabetes Association (ADA) criteria:
Show all 9Show fewer
- Fasting plasma glucose >= 126 mg/dL
- 2 hour plasma glucose >= 200 mg/dL following a 75 gram (1.75g/kg if less than 40kg) oral glucose load, or
- Diabetic symptoms with a random plasma glucose >= 200 mg/dL
Who cannot join
- Pregnant at time of enrollment, women in their reproductive years who do not use an effective method of birth control, and women currently nursing or lactating within 6 weeks of having completed nursing.
- Known infectious liver disease
- Known HIV infection
- Current alcohol or substance abuse
- Active tuberculosis
- Use of anorexigenic drugs
- Other conditions which in the opinion of the clinical investigators would impede completion of the study.
- Subjects who have a known hypersensitivity to E. Coli derived proteins.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase II Trial of Effect of Metreleptin Therapy in Severe Insulin Resistance
Study Description:
Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control.
Read more
Objectives:
Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia.
Endpoints:
Primary Endpoint: Hemoglobin A1c.
Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.
Study Population:
20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.
Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:
NIH Clinical Center
Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).
Read the detailed description
Study Description:
Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control.
Objectives:
Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia.
Endpoints:
Primary Endpoint: Hemoglobin A1c.
Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.
Study Population:
20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.
Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:
NIH Clinical Center
Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).
- Conditions
- Severe Insulin Resistance
- Being tested
- Metreleptin
- Keywords
- Rabson Mendenhall, Type B Insulin Resistance, Type A Insulin Resistance
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetreleptinDrug
Administered SC twice/day to achieve physiological concentrations that will be effective in improving the severe state of insulin resistance seen in patients with genetic defects on their insulin receptor mutation
| Study group | Role | What they receive |
|---|---|---|
| Leptin Treatment | Experimental | 300 mg of study drug administered via subcutaneous (SC) injections. Receives: Drug: Metreleptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HbA1C
Change in HbA1C at month 12 from baseline.
Measured: Change at month 12 from baseline
Secondary outcomes (2)
Change in Fasting Insulin Level
Change in fasting insulin level at month 12 from baseline
Measured: Change at month 12 from baseline
Change in Fasting Blood Glucose
Change in fasting blood glucose at month 12 from baseline.
Measured: Change at month 12 from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2004 (estimated)
- Study start21 Aug 2003
- Primary completion23 Oct 2019
- Study completion1 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Severe Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rebecca J Brown, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00085982
- Sponsor's protocol ID
- 030257
- Other IDs
- 03-DK-0257
- Status last verified
- Dec 2024
- First submitted
- 18 Jun 2004
- Last updated
- 30 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.
PubMed 32191645Okawa MC, Tuska RM, Lightbourne M, Abel BS, Walter M, Dai Y, Cochran E, Brown RJ. Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e96-e106. doi: 10.1210/clinem/dgad491.
PubMed 37595266Okawa MC, Cochran E, Lightbourne M, Brown RJ. Long-Term Effects of Metreleptin in Rabson-Mendenhall Syndrome on Glycemia, Growth, and Kidney Function. J Clin Endocrinol Metab. 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782.
PubMed 34718628Brown RJ, Cochran E, Gorden P. Metreleptin improves blood glucose in patients with insulin receptor mutations. J Clin Endocrinol Metab. 2013 Nov;98(11):E1749-56. doi: 10.1210/jc.2013-2317. Epub 2013 Aug 22.
PubMed 23969187
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Effect of Metreleptin Therapy in Severe Insulin Resistance
- ClinicalTrials.gov ID
- NCT00085982
- Acronym / sponsor ID
- 030257
- Conditions
- Severe Insulin Resistance
- Keywords
- Rabson Mendenhall, Type B Insulin Resistance, Type A Insulin Resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 11 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 21 Aug 2003 (actual)
- Primary completion
- 23 Oct 2019 (actual)
- Study completion
- 1 Jan 2030 (estimated)
- First posted
- 21 Jun 2004 (estimated)
- Results
- Posted 15 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study Description:
Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control.
Objectives:
Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia.
Endpoints:
Primary Endpoint: Hemoglobin A1c.
Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.
Study Population:
20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.
Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:
NIH Clinical Center
Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).
Detailed description
Study Description:
Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control.
Objectives:
Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia.
Endpoints:
Primary Endpoint: Hemoglobin A1c.
Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.
Study Population:
20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.
Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:
NIH Clinical Center
Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Leptin Treatment | Experimental | Drug: Metreleptin300 mg of study drug administered via subcutaneous (SC) injections. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Provision of signed and dated informed consent form
- Male or female, aged > 5 years
- Clinically significant, severe insulin resistance caused by a known or suspected defect in the insulin receptor
- Presence of at least one of the following metabolic abnormalities:
Key exclusion criteria (8 listed)
- Pregnant at time of enrollment, women in their reproductive years who do not use an effective method of birth control, and women currently nursing or lactating within 6 weeks of having completed nursing.
- Known infectious liver disease
- Known HIV infection
- Current alcohol or substance abuse
- Active tuberculosis
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 |
|---|---|---|
| MetreleptinAdministered SC twice/day to achieve physiological concentrations that will be effective in improving the severe state of insulin resistance seen in patients with genetic defects on their insulin receptor mutation | Drug | Leptin Treatment |
Primary outcome
Change in HbA1C
Time frame: Change at month 12 from baseline
Change in HbA1C at month 12 from baseline.
2 secondary outcomes
Change in Fasting Insulin Level
Time frame: Change at month 12 from baseline
Change in Fasting Blood Glucose
Time frame: Change at month 12 from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32191645Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.
- Derived from this study: PubMed 37595266Okawa MC, Tuska RM, Lightbourne M, Abel BS, Walter M, Dai Y, Cochran E, Brown RJ. Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e96-e106. doi: 10.1210/clinem/dgad491.
- Derived from this study: PubMed 34718628Okawa MC, Cochran E, Lightbourne M, Brown RJ. Long-Term Effects of Metreleptin in Rabson-Mendenhall Syndrome on Glycemia, Growth, and Kidney Function. J Clin Endocrinol Metab. 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782.
- Derived from this study: PubMed 23969187Brown RJ, Cochran E, Gorden P. Metreleptin improves blood glucose in patients with insulin receptor mutations. J Clin Endocrinol Metab. 2013 Nov;98(11):E1749-56. doi: 10.1210/jc.2013-2317. Epub 2013 Aug 22.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Rebecca J Brown, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metreleptin in people with Severe Insulin Resistance, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 9 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 30 Jan 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in HbA1C (time frame: Change at month 12 from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00085982, which also lists 4 linked publications.
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 30 Jan 2025.