Type 1 Diabetes MellitusPhase 1/2NCT03919617

Metabolic Pathways of GRA in Patients With Type 1 Diabetes

A Phase 1/2 study testing REMD-477 in people with Type 1 Diabetes Mellitus, run by University of California, San Diego at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

A pilot study for individuals with Type 1 Diabetes who are willing to add a GRA (Glucagon Receptor Antagonist) to their current Diabetes treatment regimen. There will be 10 study visits over the course of approximately 8 weeks, with 4 weeks of once weekly, subcutaneous GRA (REMD-477) injection. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Type 1 Diabetes Mellitus
What is being tested?: REMD-477
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: 1 siteUnited States
Study dates: 1 Jul 2019to 31 May 2022
Phase: Phase 1/2
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
No healthy volunteers
Adult, Older adult

Who may be able to join

Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;
Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study and for an additional 3 months after the end of dosing with the investigational product;
Male subjects must be willing to use clinically acceptable method of contraception during the entire study and for an additional 6 months after the end of the treatment period;
Diagnosed with Type 1 diabetes based on clinical history or as defined by the current American Diabetes Association (ADA) criteria for > 5 years;
Treatment with a stable insulin regimen (< 1u/kg per day) for at least 8 weeks before screening with continuous subcutaneous insulin infusion (CSII) via an insulin pump;
HbA1c ≤ 10 % at screening;
A minimum weight of 50kg;
Able to provide written informed consent approved by an Institutional Review Board (IRB).

Who cannot join

History or evidence of clinically-significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
History of pancreatitis, medullary thyroid carcinoma and/or liver disease;
Clinically significant diagnosis of anemia;
Body Mass Index (BMI) < 18.5 kg/m2 and/or weight less than 50kg;
Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion;
Current or recent (within 1 month of screening) use of diabetes medications other than insulin;

Show all 10Show fewer

Women who are pregnant or lactating/breastfeeding;
Subjects for whom an MRI is contraindicated;
Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.

Trial locations and contacts

1 site in 1 country.

United States1 site

UC San Diego Altman Clinical & Translational Research Institute
La Jolla, California, 92037

Other trials in United States

About this study

Official title: The Effects of a Glucagon Receptor Antagonist (GRA) on Non-Glucose Metabolic Pathways in Patients With Type 1 Diabetes (Pilot Study)

Read the detailed description

This single-center, open label, multi-dose study is designed to elicit pilot data for a larger project. To accomplish the specific aims proposed, a single clinical trial will be conducted in which a maximum of 10 subjects with T1D, who are otherwise healthy, will be treated with REMD-477 for 4 weeks at a dose of 70mg (administered subcutaneously each week) with assessments done pre- and post-therapy. There is no comparator, nor is there any placebo in the study. In addition, there is no randomization, all subjects will receive the same 4 weeks of 70mg, once weekly dose of REMD-477.

There will be 10 study visits as outlined below:

Screening - Complete medical history and physical exam, review of current medications, height/weight, vital signs, and fasting laboratory (blood and urine) tests.
Visit 1 - Participants that meet screening criteria will be provided deuterated (heavy) water to consume overnight. Participants will ingest heavy water (2H2O) overnight in three equal doses (total 3ml/kg/body water). Participants will also undergo an MRI to evaluate hepatic (liver) fat content as well as total body composition.
Visit 2 - Following Visit 1, participants will return to the clinic the next morning in the fasting state (8 hours) and after completing the heavy water consumption. Blood samples will be drawn for baseline amino acid levels as well as samples of serum, plasma, PBMCs, and extracted RNA stored for future metabolomics and genetic testing. Indirect calorimetry (IDC) will be performed to provide baseline resting energy expenditure (REE). Upon completion of IDC, participants will be given a 0.15 u/kg dose of rapid acting insulin and 15 minutes afterwards will ingest a 75g glucose and 25g fructose drink. Participants will then have samples collected over 6 hours to quantify isotope enrichment in plasma water as well as triglyceride isolated from VLDL. Repeat IDC will be performed 2 hours after consumption of the drink.
Visit 3 - Insulin withdrawal challenge and injection #1 of REMD-477. Participants will suspend insulin delivery and remove insulin pump. Blood sugars and ketones will be monitored for up to 6 hours.
Visit 4 - Injection #2 of REMD-477.
Visit 5 - Injection #3 of REMD-477.
Visit 6 - Injection #4 of REMD-477.
Visit 7 - Provide heavy water and complete MRI scan #2.
Visit 8 - Repeat all Visit 2 procedures.
Visit 9 - Repeat all Visit 3 procedures.
Visit 10 - Safety follow-up visit that includes physical exam, vitals, blood and urine sample collection.

Conditions: Type 1 Diabetes Mellitus
Being tested: REMD-477
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.

REMD-477Drug
4-Week, open-label, once weekly subcutaneous injection with 70mg REMD-477.

Study groups in NCT03919617
Study group	Role	What they receive
Open-Label REMD-477	Experimental	Not described Receives: Drug: REMD-477

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Beta-hydoxybutyrate (BHB) Level
The change from baseline in peak BHB production as measured by the insulin withdrawal challenge.
Measured: 4-Weeks
Rate of De Novo Lipogenesis (DNL)
Change from baseline in disrupted glucagon signaling as measured by the glucose challenge and deuterated water ingestion.
Measured: 4-Weeks
Rate of Hepatic Steatosis
Changes from baseline in hepatic steatosis as measured by the glucose challenge and deuterated water ingestion.
Measured: 4-Weeks
Rate of Resting Energy Expenditure (REE)
Change from baseline REE as measured by the glucose challenge and deuterated water ingestion.
Measured: 4-Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 201931 May 2022

First posted18 Apr 2019
Study start1 Jul 2019
Primary completion31 Jul 2021
Study completion31 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by University of California, San DiegoThe 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 1/2
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Model description: Single-center, open label, multi-dose study.
Masking: None (open label)
Enrolment: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03919617
Sponsor's protocol ID: UC-MEDJP-02
Status last verified: Jul 2022
First submitted: 15 Apr 2019
Last updated: 15 Jul 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Type 1 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effects of a Glucagon Receptor Antagonist (GRA) on Non-Glucose Metabolic Pathways in Patients With Type 1 Diabetes (Pilot Study)
ClinicalTrials.gov ID: NCT03919617
Acronym / sponsor ID: UC-MEDJP-02
Conditions: Type 1 Diabetes Mellitus
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 4 participants (actual)
Lead sponsor: University of California, San DiegoUniversity, hospital or other
Collaborators: REMD Biotherapeutics, Inc.
Study start: 1 Jul 2019 (actual)
Primary completion: 31 Jul 2021 (actual)
Study completion: 31 May 2022 (actual)
First posted: 18 Apr 2019 (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.

Detailed description

There will be 10 study visits as outlined below:

Screening - Complete medical history and physical exam, review of current medications, height/weight, vital signs, and fasting laboratory (blood and urine) tests.
Visit 1 - Participants that meet screening criteria will be provided deuterated (heavy) water to consume overnight. Participants will ingest heavy water (2H2O) overnight in three equal doses (total 3ml/kg/body water). Participants will also undergo an MRI to evaluate hepatic (liver) fat content as well as total body composition.
Visit 2 - Following Visit 1, participants will return to the clinic the next morning in the fasting state (8 hours) and after completing the heavy water consumption. Blood samples will be drawn for baseline amino acid levels as well as samples of serum, plasma, PBMCs, and extracted RNA stored for future metabolomics and genetic testing. Indirect calorimetry (IDC) will be performed to provide baseline resting energy expenditure (REE). Upon completion of IDC, participants will be given a 0.15 u/kg dose of rapid acting insulin and 15 minutes afterwards will ingest a 75g glucose and 25g fructose drink. Participants will then have samples collected over 6 hours to quantify isotope enrichment in plasma water as well as triglyceride isolated from VLDL. Repeat IDC will be performed 2 hours after consumption of the drink.
Visit 3 - Insulin withdrawal challenge and injection #1 of REMD-477. Participants will suspend insulin delivery and remove insulin pump. Blood sugars and ketones will be monitored for up to 6 hours.
Visit 4 - Injection #2 of REMD-477.
Visit 5 - Injection #3 of REMD-477.
Visit 6 - Injection #4 of REMD-477.
Visit 7 - Provide heavy water and complete MRI scan #2.
Visit 8 - Repeat all Visit 2 procedures.
Visit 9 - Repeat all Visit 3 procedures.
Visit 10 - Safety follow-up visit that includes physical exam, vitals, blood and urine sample collection.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Single-center, open label, multi-dose study.

Arm	Type	Receives
Open-Label REMD-477	Experimental	Drug: REMD-477

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;
Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study and for an additional 3 months after the end of dosing with the investigational product;
Male subjects must be willing to use clinically acceptable method of contraception during the entire study and for an additional 6 months after the end of the treatment period;
Diagnosed with Type 1 diabetes based on clinical history or as defined by the current American Diabetes Association (ADA) criteria for > 5 years;
Treatment with a stable insulin regimen (< 1u/kg per day) for at least 8 weeks before screening with continuous subcutaneous insulin infusion (CSII) via an insulin pump;

Key exclusion criteria (10 listed)

History or evidence of clinically-significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
History of pancreatitis, medullary thyroid carcinoma and/or liver disease;
Clinically significant diagnosis of anemia;
Body Mass Index (BMI) < 18.5 kg/m2 and/or weight less than 50kg;
Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion;

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
REMD-4774-Week, open-label, once weekly subcutaneous injection with 70mg REMD-477.	Drug	Open-Label REMD-477

Primary outcome

Change in Beta-hydoxybutyrate (BHB) Level
Time frame: 4-Weeks
The change from baseline in peak BHB production as measured by the insulin withdrawal challenge.
Rate of De Novo Lipogenesis (DNL)
Time frame: 4-Weeks
Change from baseline in disrupted glucagon signaling as measured by the glucose challenge and deuterated water ingestion.
Rate of Hepatic Steatosis
Time frame: 4-Weeks
Changes from baseline in hepatic steatosis as measured by the glucose challenge and deuterated water ingestion.
Rate of Resting Energy Expenditure (REE)
Time frame: 4-Weeks
Change from baseline REE as measured by the glucose challenge and deuterated water ingestion.

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 15 Jul 2022.
Individual participant dataSharing planned: No

Related trials for Type 1 Diabetes Mellitus

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Obesity, Overweight
RecruitingPhase 1
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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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing REMD-477 in people with Type 1 Diabetes Mellitus, run by University of California, San Diego 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 8 inclusion and 10 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 15 Jul 2022. 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 combined 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.

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?

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?

Change in Beta-hydoxybutyrate (BHB) Level (time frame: 4-Weeks). The study lists 4 primary outcomes in all. 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 NCT03919617.

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 15 Jul 2022.