Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-001115-73
    Sponsor's Protocol Code Number:Regenerate-1
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-04-20
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSweden - MPA
    A.2EudraCT number2018-001115-73
    A.3Full title of the trial
    A Phase I/II, 2-Arm, Open Label, Single Centre Study to Investigate the Safety and Effect of Oral GABA Therapy on β-cell Regeneration in Type 1-diabetes Patients
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Open label pilot trial to evaluate safety and diabetes status upon oral treatment with GABA in patients with longstanding type-1 diabetes.
    A.4.1Sponsor's protocol code numberRegenerate-1
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUppsala University Hospital
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportUppsala University, Diamyd Medical AB, Other applications TBD
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUppsala University Hospital
    B.5.2Functional name of contact pointPer-Ola Carlsson
    B.5.3 Address:
    B.5.3.1Street AddressDiv. Endocrinology and Diabetology, Uppsala University Hospital
    B.5.3.2Town/ cityUppsala
    B.5.3.3Post code75185
    B.5.3.4CountrySweden
    B.5.6E-mailper-ola.carlsson@mcb.uu.se
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRemygen
    D.3.2Product code γ-aminobutyric Acid (GABA)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Alprazolam Orion 0,5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderOrion Corporation
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAlprazolam Orion 0,5 mg
    D.3.2Product code Alprazolam
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Type 1 diabetes
    Typ 1 diabetes
    E.1.1.1Medical condition in easily understood language
    Type 1 diabetes
    Typ 1 diabetes
    E.1.1.2Therapeutic area Diseases [C] - Hormonal diseases [C19]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10067584
    E.1.2Term Type 1 diabetes mellitus
    E.1.2System Organ Class 10027433 - Metabolism and nutrition disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the acute and long-term safety of oral GABA treatment.
    E.2.2Secondary objectives of the trial
    The secondary objectives are to evaluate the different effect between the three treatment groups. As well as to analyze the outcome of oral GABA treatment, with or without combination with alprazolam treatment, on regaining endogenous insulin secretion as measured by C-peptide, overall diabetes status, serum levels of GABA, effects on the immune system and quality of life (QoL) of the patients (using the DTSQ and RAND-36 questionnaires).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Informed consent given by patients according to national regulations
    2. Type 1 diabetes diagnosed ≥ 5 years at the time of screening
    3. Must have been diagnosed with Type 1-diabetes before the age of 25
    4. Age ≥18 and ≤50
    5. Fasting c-peptide levels should be in the range from not detectable levels up to <0.12 nmol/L
    6. For males of childbearing potential adequate contraception is as follows:
    a. condom (male)
    b. abstinence from heterosexual intercourse
    c. female partner using contraception as below listed:
    -oral (except low‐dose gestagen (lynestrenol and norestisteron)), 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
    E.4Principal exclusion criteria
    1. Females of child-bearing potential
    2. Previous or current treatment with immunosuppressant therapy (although topical and inhalation steroids are accepted)
    3. Treatment with any oral or injected anti-diabetic medications other than insulin
    4. Patients on medications which may disturb GABA action, such as Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
    5. HbA1c > 90 mmol/mol
    6. eGFR <60 ml/min
    7. 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).
    8. Known cancer disease
    9. Known sleeping apnea or pulmonary disorder with carbon dioxide retention in blood
    10. Previous history of pancreatitis or other exocrine pancreatic disorder
    11. A history of epilepsy, myasthenia gravis, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
    12. A history of alcohol or drug abuse
    13. A significant illness other than diabetes within 2 weeks prior to first dosing
    14. Known human immunodeficiency virus (HIV) or hepatitis
    15. Females who are breastfeeding
    16. Males not willing to use adequate contraception during the study period.
    17. Known hypersensitivity against benzodiazepins or any excipients of study drugs
    18. Participation in other clinical trials with a new chemical entity within 3 months or 5 half-lives of the new chemical entity, whatever longest.
    19. Inability or unwillingness to comply with the provisions of this protocol
    20. 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.
    E.5 End points
    E.5.1Primary end point(s)
    • Number of AEs/SAEs possibly or probably related to GABA treatment or GABA treatment in combination with Alprazolam
    • Changes in laboratory parameters, physical examinations and vital signs over time vs baseline values
    E.5.1.1Timepoint(s) of evaluation of this end point
    After 6 months of treatment
    E.5.2Secondary end point(s)
    • Difference in C-peptide (Area Under the Curve [AUC]mean 0-120 min) during a Mixed Meal Tolerance Test (MMTT) between baseline and after 3 months of treatment, 6 months of treatment and the follow-up visit respectively for all treatments (Low dose daily oral GABA treatment, High dose daily oral GABA treatment, High dose oral GABA in combination with Alprazolam treatment).
    • Difference in C-peptide (Area Under the Curve [AUC]mean 0-120 min) during an MMTT between baseline and after 3 months of treatment, 6 months of treatment and the follow-up visit respectively for all treatments. Analyzed with an ultra-sensitive ELISA.
    • Difference in maximum stimulated C-peptide during an MMTT between baseline and after 3 months of treatment, 6 months of treatment and the follow-up visit respectively for all treatments.
    • Difference in maximum stimulated C-peptide during an MMTT between baseline and after 3 months of treatment, 6 months of treatment and the follow-up visit respectively for all treatments. Analyzed with an ultra-sensitive ELISA.
    • Difference between the treatments in difference in C-peptide (Area Under the Curve [AUC]mean 0-120 min) during an MMTT between baseline and after 3 months of treatment, 6 months of treatment and the follow-up visit.
    • Difference in glucagon (Area Under the Curve [AUC]mean 0-120 min) during an Hypoglycemic Clamp between baseline and 6 months of treatment for all treatments.
    • Difference between treatments in difference in glucagon (Area Under the Curve [AUC]mean 0-120 min) during an Hypoglycemic Clamp between baseline and 6 months of treatment.
    • Variables that indicate diabetes status such as plasma C-peptide, glucagon, proinsulin, proinsulin/C-peptide, glucagon like-peptide 1, lipids Hemoglobin A1c (HbA1c) and insulin adjusted HbA1c (IDAAC). Daily exogenous insulin consumption, variability of blood sugar, and number of self-reported hypoglycemia.
    • Variables that indicate effects on the immune system such as serum autoantibodies (and isotypes) to GAD65 and Islet Antigen-2 and a general profiling of the immune cells in the blood.
    • Analysis of GABA plasma levels after 3 and 6 months of treatment and at the follow-up visit.
    • Measurements of patient QoL by questionnaire.
    E.5.2.1Timepoint(s) of evaluation of this end point
    After 3 and 6 months of treatment and at follow up (1 month after end of treatment).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Safety
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 36
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state36
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 36
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-06-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-09-27
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 23:44:20 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA