Oral ileum-targeted controlled-release nicotinic acid to reverse prediabetes

A Phase II, Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Oral Controlled-ileal-release Nicotinic Acid (CIR-NA) for Inducing Remission in Subjects With Prediabetes

This trial tests whether taking a daily oral ileum-targeted controlled-release nicotinic acid pill for 26 weeks can help adults with prediabetes return to normal blood sugar and remains safe.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 390 (estimated)
• Ages: 18 Years to 79 Years
• Sex: All
• Sponsor: University Hospital Schleswig-Holstein (Academic / other)
• Locations: 2 sites (Kiel and 1 other locations)
• Trial ID: NCT07286747 on ClinicalTrials.gov

What this trial studies

This multi-center, randomized, double-blind, placebo-controlled Phase 2 trial compares two daily doses (100 mg and 200 mg) of controlled-ileal-release nicotinic acid (CIR-NA) to placebo over a 26-week intervention plus a 4-week follow-up. Adults with prediabetes and BMI ≥20 kg/m² are randomized 1:1:1 across the three arms, receiving one indistinguishable tablet daily with regular clinic visits for safety labs, 12-lead ECGs, vitals, and physical exams. The trial combines standardized lifestyle recommendations with blinded drug/placebo exposure to measure remission of prediabetes to normoglycemia and to confirm safety observations from Phase 1. About 390 participants will be enrolled with visits at week 1 and then every 4 weeks during treatment.

Who should consider this trial

Good fit: Adults aged 18–79 years with BMI ≥20 kg/m² who meet EASD/DDG criteria for prediabetes (but not diabetes) and have a MASLD fibrosis score ≥ -1.455 are ideal candidates.

Not a fit: People with established type 2 diabetes, significant renal impairment (GFR <60 ml/min/1.73 m²), hepatic dysfunction, uncontrolled comorbidities, or those unable to attend the German study sites are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, CIR-NA could offer a gut-targeted pill that helps people with prediabetes return to normal glucose levels and reduce progression to type 2 diabetes.

How similar studies have performed: The ileal-targeted nicotinic acid approach is relatively novel: Phase 1 data suggest acceptable safety, but large randomized data showing remission of prediabetes are lacking.

Eligibility criteria

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.

Where this trial is running

Kiel and 1 other locations

• University Medical Center Schleswig-Holstein, Campus Kiel — Kiel, Germany (Recruiting)
• University of Leipzig Medical Center — Leipzig, Germany (Recruiting)

Study contacts

• Principal investigator: Matthias Laudes, Prof. Dr. — University Medical Center Schleswig-Holstein, Campus Kiel
• Study coordinator: Corinna Geisler, PhD

Conditions Prediabetes