Vitamin D and Type 2 Diabetes - Treat-To-Target

NCT07448974 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: D2d-TTT
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study tests whether taking a weekly dose of vitamin D, with the dose adjusted to reach a target blood vitamin D level, can help control blood sugar levels in adults at high risk of developing type 2 diabetes (prediabetes). Research suggests that vitamin D may play a role in blood sugar control. The goal of this study is to see whether adjusting the dose of vitamin D to reach a specific blood vitamin D level improves blood sugar control compared with a placebo (a look-alike pill without vitamin D). One hundred adults aged 30 to 74 with prediabetes will take part. Participants will be randomly assigned (by chance) to receive either weekly vitamin D supplements or a placebo. Neither the participants nor the research team will know which group a participant is in during the study. Participants in the vitamin D group will start with one specific dose. After three months, a blood test will be used to decide whether the dose should stay the same or be increased to reach the target vitamin D level. Participants in the placebo group will continue taking the placebo each week. All participants will be followed for about 18 months. During the study, they will attend scheduled study visits, have blood tests, and wear a continuous glucose monitor, a small device that measures blood sugar levels throughout the day and night. The research team will also make periodic phone calls to check on health changes, medication use, and study participation. The main outcome of the study is the proportion of time that the participants' blood sugar levels remains in a healthy range.

Conditions

Prediabetes; Type 2 Diabetes (T2DM)

Keywords

vitamin D; cholecalciferol; continuous glucose monitoring; diabetes prevention; prediabetes; type 2 diabetes

Outcome Measures

Primary Outcomes (2)

• Time-in-normoglycemia 140

  The cumulative proportion of time that a participant's glucose level is below 140 mg/dL at each CGM measurement period.

  Assessed every 6 months from enrollment to the end of the study at 18 months.

• Time-In-Normoglycemia 126

  The cumulative proportion of time that a participant's glucose level is below 126 mg/dL at each CGM measurement period.

  Assessed every 6 months from enrollment to the end of the study at 18 months.

Secondary Outcomes (7)

• Mean glycemia (mg/dL)

  Assessed every 6 months from enrollment to the end of the study at 18 months

• Glycemic variability

  Assessed every 6 months from enrollment to the end of the study at 18 months

• Hemoglobin A1c (%)

  Assessed every 6 months from enrollment to the end of the study at 18 months.

• Fasting plasma glucose (mg/dL)

  Assessed every 6 months from enrollment to the end of the study at 18 months.

• Atherosclerotic cardiovascular risk

  Assessed at baseline, month 12 and month 18

Other Outcomes (2)

• Insulin resistance

  Assessed at baseline, 12 months, and 18 months.

• Insulin secretion

  Assessed from enrollment to the end of study at 18 months.

Study Arms (2)

Vitamin D

ACTIVE COMPARATOR

Participants will receive oral vitamin D (cholecalciferol) once weekly throughout the study.

Drug: Vitamin D (Cholecalciferol )

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive an oral placebo taken once weekly throughout the study.

Drug: Placebo

Interventions

Vitamin D (Cholecalciferol ) DRUG

Vitamin D (cholecalciferol) will be administered orally once weekly for approximately 18 months. The vitamin D will be provided in liquid form in an ampule. Participants in the intervention group will begin with a dose of 25,000 IU per week. A blood vitamin D level will be measured at 3 months, and the dose will be increased to 50,000 IU per week for participants whose results are below the study target.

Vitamin D

Placebo DRUG

Placebo will be administered orally once weekly for approximately 18 months. The placebo will be provided in an ampule and will be matched in appearance, dosing schedule, and duration to the active study medication.

Placebo

Eligibility Criteria

• Age: 30 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• High-risk prediabetes ("at high risk for type 2 diabetes") defined by meeting the following 2 prediabetes criteria established by the American Diabetes Association (ADA) in the 2010 clinical practice guidelines:
• Fasting plasma glucose (FPG) 100-125 mg/dL, inclusive
• Hemoglobin A1c (HbA1c) 5.7-6.4%, inclusive
• Age 30-74 years, inclusive
• Body Mass Index ≥ 23.0 and ≤ 35.0 kg/m2
• Provision of signed and dated written informed consent prior to any study procedures.

You may not qualify if:

• History of diabetes (ICD10 diabetes code E08.X through E13.X) or meeting a diabetes glycemic criterion at screening, as defined by the ADA guidelines (FPG ≥ 126 mg/dL or HbA1c ≥ 6.5%).
• History (past 2 years) of hyperparathyroidism, symptomatic or asymptomatic (i.e., radiographic) nephrolithiasis or hypercalcemia.
• Any medical condition (past 2 years) that in the opinion of the site investigator may increase risk for nephrolithiasis or hypercalcemia during the trial (e.g., sarcoidosis).
• If older than 70 years, history (past 1 year) of a fall.
• Use of tanning devices within 12 weeks of the baseline visit and unwilling to stop use of tanning devices for the duration of the study.
• Medications and Supplements
• Use (past 6 months) of hypoglycemic pharmacotherapy (oral or injectable medication approved by the FDA for type 2 diabetes) for any condition (e.g., prediabetes, diabetes, polycystic ovarian syndrome, MASLD, sleep apnea) or any other medication that may affect glycemia (e.g., hydroxychloroquine)
• Current use of medications approved by the FDA for weight management (e.g., incretin receptor agonists) or planned use during the study.
• Use of supplements containing vitamin D at total doses higher than 1000 IU/day within 8 weeks of the baseline visit and unwillingness to limit vitamin D supplementation dosage to no higher than 1000 IU/day during the study. Because supplements vary widely in vitamin D content (e.g., may include cod liver or cod liver oi), participants will bring all supplements to the site for a review by the research team.
• Use of supplements containing calcium at total doses higher than 600 mg/day within 1 week of the baseline visit and unwillingness to limit calcium supplementation dosage to no higher than 600 mg/day during the study.
• Current use of medications or conditions (e.g., untreated celiac disease) that would interfere with the absorption or metabolism of vitamin D.
• Use of an anticonvulsant drug started within 6 months of screening. Stable regimen of anticonvulsants is allowed.
• History of intolerance to vitamin D supplements, allergic to any content of the study drug or unwilling to take vitamin D supplements (e.g., someone who eats a vegan diet and would object to the cholecalciferol ingredient which is produced from cholesterol extracted from sheep wool harvested from healthy living sheep).
• Other Medical History
• Severe symptomatic cardiovascular disease based on history (unstable angina, dyspnea on exertion, paroxysmal nocturnal dyspnea, arrhythmia, congestive heart failure NYHA class II or higher, claudication)

Sponsors & Collaborators

• Tufts Medical Center: lead
• Abiogen Pharma: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (3)

• Chatterjee R, Davenport CA, Vickery EM, Johnson KC, Kashyap SR, LeBlanc ES, Nelson J, Dagogo-Jack S, Pittas AG, Hughes BD; D2d Research Group. Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study. Am J Clin Nutr. 2023 Jul;118(1):59-67. doi: 10.1016/j.ajcnut.2023.03.021. Epub 2023 Mar 29.

  PMID: 37001590 BACKGROUND

• Pittas AG, Kawahara T, Jorde R, Dawson-Hughes B, Vickery EM, Angellotti E, Nelson J, Trikalinos TA, Balk EM. Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med. 2023 Mar;176(3):355-363. doi: 10.7326/M22-3018. Epub 2023 Feb 7.

  PMID: 36745886 BACKGROUND

• Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O'Neil P, Park J, Peters A, Phillips LS, Pratley R, Raskin P, Rasouli N, Robbins D, Rosen C, Vickery EM, Staten M; D2d Research Group. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med. 2019 Aug 8;381(6):520-530. doi: 10.1056/NEJMoa1900906. Epub 2019 Jun 7.

  PMID: 31173679 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Prediabetic State; Diabetes Mellitus, Type 2

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Central Study Contacts

Tufts Medical Center Endocrine Research Team

CONTACT

617-636-3232; endocrine-research@tuftsmedicine.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2026
• First Posted: March 4, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2031
• Last Updated: March 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)