Type 1 Diabetes MellitusPhase 1/2NCT03635437
Evaluation of Safety and Diabetes Status Upon Oral Treatment With GABA in Patients With Longstanding Type-1 Diabetes
A Phase 1/2 study testing Gamma-Aminobutyric Acid (GABA) and Alprazolam in people with Type 1 Diabetes Mellitus, run by Per-Ola Carlsson at 1 site in Sweden.
Trial summary
The main goal of this study is to find a reasonably safe and tolerable treatment for adult patients with type 1-diabetes and that regain some of the endogenous insulin secretion, improve the patients' quality of life (QoL) and reduce the risk of both short- and long-term complications. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Gamma-Aminobutyric Acid (GABA) and Alprazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteSweden
- Study dates
- 5 Sep 2018to 27 Sep 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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Informed consent given by patients according to national regulations
- Type 1 diabetes diagnosed ≥ 5 years at the time of screening
- Must have been diagnosed with Type 1-diabetes before the age of 25
- Age ≥18 and ≤50
- Fasting c-peptide levels should be in the range from not detectable levels up to <0.12 nmol/L
- For males of childbearing potential adequate contraception is as follows:
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- condom (male)
- abstinence from heterosexual intercourse
- female partner using contraception as below listed:
- oral (except low-dose gestagen (lynestrenol and norethisterone)), injectable, or implanted hormonal contraceptives
- combined (estrogen and progestogen containing)
- oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
- intrauterine device
- intrauterine hormone-releasing system (for example, progestin-releasing coil)
- bilateral tubal occlusion
Who cannot join
- Females of child-bearing potential
- Previous or current treatment with immunosuppressant therapy (although topical and inhalation steroids are accepted)
- Treatment with any oral or injected anti-diabetic medications other than insulin
- Patients on medications which may disturb GABA action, such as Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
- HbA1c > 90 mmol/mol
- eGFR <60 ml/min
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- Increased plasma concentrations of alanine aminotransferase (>0.75 μkatl/l for females or >1.1 μkat/l for males) and/or aspartate aminotransferase (>0.60 μkat/l for females or >0.75μkat/l for males).
- Known cancer disease
- Known sleeping apnea or pulmonary disorder with carbon dioxide rentention in blood
- Previous history of pancreatitis or other exocrine pancreatic disorder
- A history of epilepsy, myasthenia gravis, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
- A history of alcohol or drug abuse
- A significant illness other than diabetes within 2 weeks prior to first dosing
- Known human immunodeficiency virus (HIV) or hepatitis
- Females who are breastfeeding
- Males not willing to use adequate contraception during the study period.
- Known hypersensitivity agains benzodiazepins or any excipients of study drugs
- Participation in other clinical trials with a new chemical entity within 3 months or 5 half-lives of the new chemical entity, whatever longest.
- Inability or unwillingness to comply with the provisions of this protocol
- Deemed by the investigator not being able to follow instructions and/or follow the study protocol or other reasons that, at the investigator's discretion, could affect the subject's current clinical condition during study procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II, 3-Arm, Open Label, Single Centre Study to Investigate the Safety and Effect of Oral GABA Therapy on Beta-Cell Regeneration in Type 1-diabetes Patients
The main goal of this study is to find a reasonably safe and tolerable treatment for adult patients with type 1-diabetes and that regain some of the endogenous insulin secretion, improve the patients' quality of life (QoL) and reduce the risk of both short- and long-term complications. The hypothesis tested is that oral GABA treatment with the newly developed compound Remygen will be safe and induce regain of some endogenous insulin secretion in adult patients with type 1-diabetes diagnosis for more than five years. The first part of the study will include 6 patients and be performed as a Safety and Dose Escalation study in three steps. The main study is a three-arm, open label, single center, clinical trial. Eligible patients will be randomized into one of three active treatment arms to receive oral GABA treatment for 6 months.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Gamma-Aminobutyric Acid (GABA), Alprazolam
- Keywords
- Remygen, GABA
- 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.
Gamma-Aminobutyric Acid (GABA)Drug
Also called GABA (Remygen)
Patients eligible for the main study will be randomized in a 1:1:1 ratio stratified by the C-peptide level to receive 200 mg of GABA (Remygen) for 6 months, 600 mg of GABA (Remygen) for 6 months, or Alprazolam 0.5 mg combined with GABA 600 mg (Remygen) for 3 months followed by treatment with GABA 600 mg (Remygen) only for another 3 months. The start of the arms with high dose GABA will be delayed and started first after that a data safety monitoring board has evaluated and approved the safety data of the first 4 patients included in the arm with low dose GABA. All patients will continue to receive intensive insulin treatment from their personal physicians during the whole study period.
AlprazolamDrug
Patients eligible for the main study will be randomized in a 1:1:1 ratio stratified by the C-peptide level to receive 200 mg of GABA (Remygen) for 6 months, 600 mg of GABA (Remygen) for 6 months, or Alprazolam 0.5 mg combined with GABA 600 mg (Remygen) for 3 months followed by treatment with GABA 600 mg (Remygen) only for another 3 months. The start of the arms with high dose GABA will be delayed and started first after that a data safety monitoring board has evaluated and approved the safety data of the first 4 patients included in the arm with low dose GABA. All patients will continue to receive intensive insulin treatment from their personal physicians during the whole study period.
| Study group | Role | What they receive |
|---|---|---|
| Low dose gamma-aminobutyric acid (GABA) | Experimental | Oral GABA treatment 200 mg daily for 6 months Receives: Drug: Gamma-Aminobutyric Acid (GABA) |
| High dose gamma-aminobutyric acid (GABA) | Experimental | Oral GABA treatment 600 mg daily for 6 months Receives: Drug: Gamma-Aminobutyric Acid (GABA) |
| High dose gamma-aminobutyric acid (GABA) + Alprazolam | Experimental | Oral Alprazolam treatment 0.5 mg daily combined with oral GABA treatment 600 mg daily for 3 months. Alprazolam treatment thereafter ended, and study subjects will continue with oral GABA treatment 600 mg daily only for another 3 months. Receives: Drug: Gamma-Aminobutyric Acid (GABA); Drug: Alprazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events possibly or probably related to GABA treatment
To evaluate the acute and long-term safety of oral GABA treatment. The endpoint will investigate number of adverse events possibly or probably related to GABA treatment.
Measured: 6 months
Secondary outcomes (12)
Difference in C-peptide response to mixed meal tolerance test before and directly after treatment
Difference in C-peptide (Area under the curve 0-120 min) during a mixed meal tolerance test between baseline and after 6 months of oral GABA treatment
Measured: 6 months
Difference in C-peptide response to mixed meal tolerance test during and after treatment
Difference in C-peptide (Area under the curve 0-120 min) during a mixed meal tolerance test between baseline and after 3 and and 6 months of treatment and between baseline and the follow-up visit
Measured: 7 months
Difference in maximum stimulated C-peptide to mixed meal tolerance test during and after treatment
Difference in maximum stimulated C-peptide during a mixed meal tolerance test between baseline and after 3 and 6 months of treatment and between baseline and the follow-up visit.
Measured: 7 months
Difference in C-peptide response to mixed meal tolerance test during and after treatment between treatment groups
Difference in C-peptide (Area under the curve 0-120 min) during a mixed meal tolerance test between treatment group 1 and 2 and after 3 and 6 months of treatment and between baseline and the follow-up visit
Measured: 7 months
Difference in glucagon response during a hypoglycemic clamp before and after treatment
Difference in glucagon (area under the curve) during a hypoglycemic clamp between baseline and 6 months of treatment
Measured: 7 months
Difference in glucagon response during a hypoglycemic clamp between treatment groups before and after treatment
Difference in glucagon (area under the curve) during a hypoglycemic clamp between treatment group 1 and 2 between baseline and 6 months of treatment
Measured: 7 months
Change in HbA1c by treatment
Change in HbA1c between 0,3 and 6 months of treatment and at the follow-up one month later.
Measured: 7 months
Change in exogenous insulin consumption by treatment
Change in exogenous insulin consumption between 0,3 and 6 months of treatment and at the follow-up one month later.
Measured: 7 months
Change in fasting C-peptide by treatment
Change in fasting C-peptide levels between 0,3 and 6 months of treatment and at the follow-up one month later.
Measured: 7 months
Change in variables that indicate effects on immune system
Change by treatment in variables that indicate effects on the immune system such as serum autoantibodies to GAD65 and islet antigen-2, and immune cells
Measured: 7 months
Change in GABA plasma levels
Analysis of GABA plasma levels after 0, 3 and 6 months of treatment and at the follow-up visit one month later.
Measured: 7 months
Change in diabetes treatment satisfaction questionnaire
Measurements of patient diabetes treatment satisfaction by questionnaire during study. Each of eight questions have a 7-graded scale from 0-6. 48 points are therefore maximal treatment satisfaction and comparisons will be made to score before treatment start.
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start5 Sep 2018
- Primary completion27 Sep 2022
- Study completion27 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Per-Ola Carlsson
- Sponsor type
- University, hospital or other
- Collaborators
- Diamyd Medical AB
- Responsible party
- Sponsor-investigator, Per-Ola Carlsson, Uppsala University Hospital
- Investigators
- Per-Ola Carlsson, MD, PhD, Principal investigator, Uppsala University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03635437
- Sponsor's protocol ID
- Regenerate-1 (G/P2/18/1)
- Status last verified
- Nov 2022
- First submitted
- 9 Aug 2018
- Last updated
- 2 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Espes D, Liljeback H, Hill H, Elksnis A, Caballero-Corbalan J, Carlsson PO. GABA induces a hormonal counter-regulatory response in subjects with long-standing type 1 diabetes. BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002442. doi: 10.1136/bmjdrc-2021-002442.
PubMed 34635547
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, 3-Arm, Open Label, Single Centre Study to Investigate the Safety and Effect of Oral GABA Therapy on Beta-Cell Regeneration in Type 1-diabetes Patients
- ClinicalTrials.gov ID
- NCT03635437
- Acronym / sponsor ID
- Regenerate-1 (G/P2/18/1)
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Remygen, GABA
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Per-Ola CarlssonUniversity, hospital or other
- Collaborators
- Diamyd Medical AB
- Study start
- 5 Sep 2018 (actual)
- Primary completion
- 27 Sep 2022 (actual)
- Study completion
- 27 Sep 2022 (actual)
- First posted
- 17 Aug 2018 (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.
The main goal of this study is to find a reasonably safe and tolerable treatment for adult patients with type 1-diabetes and that regain some of the endogenous insulin secretion, improve the patients' quality of life (QoL) and reduce the risk of both short- and long-term complications. The hypothesis tested is that oral GABA treatment with the newly developed compound Remygen will be safe and induce regain of some endogenous insulin secretion in adult patients with type 1-diabetes diagnosis for more than five years. The first part of the study will include 6 patients and be performed as a Safety and Dose Escalation study in three steps. The main study is a three-arm, open label, single center, clinical trial. Eligible patients will be randomized into one of three active treatment arms to receive oral GABA treatment for 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low dose gamma-aminobutyric acid (GABA) | Experimental | Drug: Gamma-Aminobutyric Acid (GABA)Oral GABA treatment 200 mg daily for 6 months |
| High dose gamma-aminobutyric acid (GABA) | Experimental | Drug: Gamma-Aminobutyric Acid (GABA)Oral GABA treatment 600 mg daily for 6 months |
| High dose gamma-aminobutyric acid (GABA) + Alprazolam | Experimental | Drug: Gamma-Aminobutyric Acid (GABA), Drug: AlprazolamOral Alprazolam treatment 0.5 mg daily combined with oral GABA treatment 600 mg daily for 3 months. Alprazolam treatment thereafter ended, and study subjects will continue with oral GABA treatment 600 mg daily only for another 3 months. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Informed consent given by patients according to national regulations
- Type 1 diabetes diagnosed ≥ 5 years at the time of screening
- Must have been diagnosed with Type 1-diabetes before the age of 25
- Age ≥18 and ≤50
- Fasting c-peptide levels should be in the range from not detectable levels up to <0.12 nmol/L
Key exclusion criteria (20 listed)
- Females of child-bearing potential
- Previous or current treatment with immunosuppressant therapy (although topical and inhalation steroids are accepted)
- Treatment with any oral or injected anti-diabetic medications other than insulin
- Patients on medications which may disturb GABA action, such as Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
- HbA1c > 90 mmol/mol
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 |
|---|---|---|
| Gamma-Aminobutyric Acid (GABA)Also: GABA (Remygen)Patients eligible for the main study will be randomized in a 1:1:1 ratio stratified by the C-peptide level to receive 200 mg of GABA (Remygen) for 6 months, 600 mg of GABA (Remygen) for 6 months, or Alprazolam 0.5 mg combined with GABA 600 mg (Remygen) for 3 months followed by treatment with GABA 600 mg (Remygen) only for another 3 months. The start of the arms with high dose GABA will be delayed and started first after that a data safety monitoring board has evaluated and approved the safety data of the first 4 patients included in the arm with low dose GABA. All patients will continue to receive intensive insulin treatment from their personal physicians during the whole study period. | Drug | High dose gamma-aminobutyric acid (GABA), High dose gamma-aminobutyric acid (GABA) + Alprazolam, Low dose gamma-aminobutyric acid (GABA) |
| AlprazolamPatients eligible for the main study will be randomized in a 1:1:1 ratio stratified by the C-peptide level to receive 200 mg of GABA (Remygen) for 6 months, 600 mg of GABA (Remygen) for 6 months, or Alprazolam 0.5 mg combined with GABA 600 mg (Remygen) for 3 months followed by treatment with GABA 600 mg (Remygen) only for another 3 months. The start of the arms with high dose GABA will be delayed and started first after that a data safety monitoring board has evaluated and approved the safety data of the first 4 patients included in the arm with low dose GABA. All patients will continue to receive intensive insulin treatment from their personal physicians during the whole study period. | Drug | High dose gamma-aminobutyric acid (GABA) + Alprazolam |
Primary outcome
Adverse events possibly or probably related to GABA treatment
Time frame: 6 months
To evaluate the acute and long-term safety of oral GABA treatment. The endpoint will investigate number of adverse events possibly or probably related to GABA treatment.
12 secondary outcomes
Difference in C-peptide response to mixed meal tolerance test before and directly after treatment
Time frame: 6 months
Difference in C-peptide response to mixed meal tolerance test during and after treatment
Time frame: 7 months
Difference in maximum stimulated C-peptide to mixed meal tolerance test during and after treatment
Time frame: 7 months
Difference in C-peptide response to mixed meal tolerance test during and after treatment between treatment groups
Time frame: 7 months
Difference in glucagon response during a hypoglycemic clamp before and after treatment
Time frame: 7 months
Difference in glucagon response during a hypoglycemic clamp between treatment groups before and after treatment
Time frame: 7 months
Change in HbA1c by treatment
Time frame: 7 months
Change in exogenous insulin consumption by treatment
Time frame: 7 months
Change in fasting C-peptide by treatment
Time frame: 7 months
Change in variables that indicate effects on immune system
Time frame: 7 months
Change in GABA plasma levels
Time frame: 7 months
Change in diabetes treatment satisfaction questionnaire
Time frame: 7 months
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 2 Nov 2022.
- Derived from this study: PubMed 34635547Espes D, Liljeback H, Hill H, Elksnis A, Caballero-Corbalan J, Carlsson PO. GABA induces a hormonal counter-regulatory response in subjects with long-standing type 1 diabetes. BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002442. doi: 10.1136/bmjdrc-2021-002442.
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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.
Per-Ola Carlsson, MD, PhD principal investigator
Uppsala University Hospital
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 Gamma-Aminobutyric Acid (GABA) and Alprazolam in people with Type 1 Diabetes Mellitus, run by Per-Ola Carlsson at 1 site in Sweden.
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 15 inclusion and 20 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 2 Nov 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 Sweden. 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?
Adverse events possibly or probably related to GABA treatment (time frame: 6 months). 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 NCT03635437, which also lists 1 linked publication.
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 2 Nov 2022.