Efficacy and Safety of Oral Controlled-release Nicotinic Acid (CIR-NA) for the Remission of Prediabetes. (CONCEPT)

NCT ID: NCT07286747

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

390 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2028-12-31

Brief Summary

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The goal of this clinical trial is to prevent the change from prediabetes (a pre-stage of type 2 diabetes mellitus (T2DM)) to T2DM in participants with prediabetes using oral CIR-NA (a nicotinic acid formulation that is designed to be released after reaching the ileum) which targeted the gut microbiota. The main questions it aims to answer are:

1. Is CIR-NA effective and does it prevent the change from prediabetes to T2DM?
2. Is the safety of CIR-NA that was observed in the Phase I clinical trial confirmed in subjects with prediabetes?

Researchers will compare CIR-NA to a placebo (a look-alike substance that contains no drug) in terms of an extended safety evaluation including safety laboratory assessments, physical examination, vital signs and 12-lead ECG.

Participants will:

Take CIR-NA or a placebo every day for 26-weeks. Visit the clinic at week 1 and subsequently once every 4 weeks for checkups and tests.

Receive standardized lifestyle recommendations regarding nutrition and physical activity during the intervention.

Detailed Description

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The study is a multi-centre, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of CIR-NA in participants with prediabetes. The trial includes a 26-week intervention period, which is expected to provide adequate time for prediabetes remission and a 4-week follow-up (FU) period.

A total of 390 male and female participants with a BMI of ≥ 20 kg/m² with prediabetes will be random-ised into three arms with 130 participants each in the CIR-NA (100 mg/d or 200 mg/d CIR-NA) and placebo groups. During the intervention, two indistinguishable tablets (CIR-NA and/or placebo) will be administered orally once daily. After screening and baseline assessment (including randomisation and IMP dispensing), 7 regular visits during treatment and one FU visit after 4 weeks are scheduled.

Conditions

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Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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CIR-NA 200

CIR-NA 200 mg once daily

Group Type ACTIVE_COMPARATOR

controlled-ileal-release nicotinic acid as multiple dose 200 mg/day

Intervention Type DRUG

130 participants will receive CIR-NA (200 mg/d). Additionally, all participants will receive standardized lifestyle recommendations regarding nutrition and physical activity.

CIR-NA Placebo

Placebo once daily

Group Type PLACEBO_COMPARATOR

controlled-ileal-release nicotinic acid as multiple dose placebo

Intervention Type DRUG

130 participants will receive placebo. Additionally, all participants will receive standardized lifestyle recommendations regarding nutrition and physical activity.

CIR-NA 100

CIR-NA 100 mg once daily

Group Type ACTIVE_COMPARATOR

controlled-ileal-release nicotinic acid as multiple dose 100 mg/day

Intervention Type DRUG

130 participants will receive CIR-NA (100 mg/d). Additionally, all participants will receive standardized lifestyle recommendations regarding nutrition and physical activity.

Interventions

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controlled-ileal-release nicotinic acid as multiple dose 100 mg/day

130 participants will receive CIR-NA (100 mg/d). Additionally, all participants will receive standardized lifestyle recommendations regarding nutrition and physical activity.

Intervention Type DRUG

controlled-ileal-release nicotinic acid as multiple dose 200 mg/day

130 participants will receive CIR-NA (200 mg/d). Additionally, all participants will receive standardized lifestyle recommendations regarding nutrition and physical activity.

Intervention Type DRUG

controlled-ileal-release nicotinic acid as multiple dose placebo

130 participants will receive placebo. Additionally, all participants will receive standardized lifestyle recommendations regarding nutrition and physical activity.

Intervention Type DRUG

Other Intervention Names

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CIR-NA 100 mg CIR-NA 200 mg Placebo

Eligibility Criteria

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Inclusion Criteria

1. Male and female participants ≥ 18 to \< 80 years of age (at the time of signing the informed consent).
2. Body mass index ≥ 20 kg/m².
3. Ability to understand and comply with the protocol.
4. Signed written informed consent.
5. Diagnosed prediabetes according to the current EASD/DDG guidelines. Prediabetes is present if at least one value is in the prediabetes range, but no value is in the T2DM range.
6. Subgroup-specific: MASLD fibrosis score ≥ -1.455.

Exclusion Criteria

1. Presence or a history of type 2 diabetes mellitus according to the current EASD/DDG guidelines.
2. Participants with relevant medical conditions (based on evaluation of medical history and screening assessments), unstable and uncontrolled underlying diseases, e.g., hypothyroidism, asthma, COPD or arterial hypertension, can be excluded per judgment of the Investigator.
3. Renal impairment (glomerular filtration rate \<60 ml/min/1.73).
4. Impairment of hepatic function (one or more of liver enzymes alanine transaminase, aspartate transaminase and gamma glutamyl transferase \[\> 3-fold compared to normal range\]).
5. Current infection with hepatitis B or C.
6. Clinically relevant abnormal findings in medical history or screening assessments which, in the opinion of the Investigator, may put the participant at risk when participating in the trial or provide difficulties in interpreting the trial data.
7. Current or history of malignancy except for completely resected basal cell carcinoma and squamous cell carcinoma of the skin.
8. Alcohol or drug abuse within the last 2 years at the discretion of the Investigator.
9. Subgroup-specific: Any circumstances which could contradict MRI and MRS imaging. For details, see Informed Consent Form (ICF) for additional examinations.
10. Regular use of any prescribed or over-the-counter medication, food supplements or herbal preparations, which cannot be terminated 3 weeks before baseline and during the full duration of the trial. Pain medication (e.g., ibuprofen or paracetamol), topical allergy medicines, hormone replacement therapies and oral contraceptives according to label are allowed. Medications in stable doses for controlling stable underlying diseases (see exclusion criterion 2) are also allowed per judgment of the Investigator.
11. Use of antibiotics (systemic or gut-acting \[non-absorbed\]) within 8 weeks prior to the first dose of IMP.
12. Long term use of higher doses of proton pump inhibitors, targeted H2-receptor antagonists or antacid formulations (i.e., doses equivalent to \> 40 mg pantoprazole per day).
13. Known hypersensitivity towards any component of the CIR-NA or placebo tablets.
14. Participation in a clinical trial (as defined in the clinical trial regulation (CTR)), currently or within 4 weeks prior to screening for this trial or intake of an IMP within the last 8 weeks or 5 half-lives (whichever is longer) prior to screening (or longer, if necessary, at the Investigator's discretion).
15. Participants under legal supervision or guardianship, including participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
16. Participants who are dependent on the Investigator or the Sponsor.
17. Pregnant or breastfeeding women.
18. Women of childbearing potential (WoCBP) not using highly effective contraception till at least 1 month after last dosing of IMP.
19. Male participants with female partners of childbearing potential who are not willing to use a highly effective contraception till at least 1 month after last dosing of IMP.
20. Any other circumstances or medical conditions which could contradict a trial participation and lead the Investigator to assess the participant as unsuitable for trial participation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Schleswig-Holstein

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthias Laudes, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Schleswig-Holstein, Campus Kiel

Locations

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University Medical Center Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Site Status

Countries

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Germany

Central Contacts

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Corinna Geisler, PhD

Role: CONTACT

+4943150022446

Matthias Laudes, Prof. Dr.

Role: CONTACT

+49 431 500 22217

Facility Contacts

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Corinna Geisler, PhD

Role: primary

+4943150022246

Other Identifiers

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LA1347/6-1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2024-519903-88-00

Identifier Type: CTIS

Identifier Source: secondary_id

CONCEPT

Identifier Type: -

Identifier Source: org_study_id