Low-Dose Radiotherapy for Alzheimer's Disease

NCT07693140 | Recruiting Phase 1 DMC

• 1 other identifier: LDRT-MIND
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of low-dose whole brain radiotherapy (WBRT) delivered as an induction course of 0.3 Gy × 10 fractions (3.0 Gy total) followed by 12 months of monthly maintenance LDRT (0.3 Gy × 10 fractions; 3.0 Gy total) in patients with Alzheimer's disease or dementia with inflammatory components

Conditions

Alzheimer Dementia; Dementia; Alzheimer; Alzheimer s Disease; Alzheimer Dementia (AD)

Keywords

LDRT; Low-dose radiotherapy; Low-dose radiation therapy; Dementia; Alzheimer

Outcome Measures

Primary Outcomes (1)

• Safety, As Measured By Incidence of Grade 3 or Higher Treatment-Related Adverse Events

  The primary endpoint is the proportion of participants who experience at least one treatment-related adverse event of Grade 3 or higher, graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events are assessed continuously and attributed to study treatment (induction plus monthly maintenance low-dose whole-brain radiotherapy) by the investigator. Feasibility is defined by an acceptable rate of Grade 3 or higher treatment-related events: 15% or lower during the Phase I lead-in (first 10 participants) and 20% or lower across the full study population (N=50). Safety is monitored continuously using a Bayesian Beta-Binomial model; the study pauses for Data Safety Monitoring Board review if the posterior probability that the true Grade 3 or higher rate exceeds 20% reaches 0.80 or greater.

  From the first induction radiotherapy fraction through 30 days after the final monthly maintenance fraction (acute monitoring period), approximately 13 to 15 months

Secondary Outcomes (1)

• Cognitive Preservation, As Measured By Change in Montreal Cognitive Assessment (MoCA) Score From Baseline to Month 12

  Baseline to Month 12, with MoCA assessed longitudinally across the maintenance period and at a standalone Month 12 cognitive endpoint visit

Study Arms (1)

Treatment Group

EXPERIMENTAL

Low dose radiotherapy in 10 induction treatments followed by 10 maintenance treatments spread across each month starting at 2 month post- induction

Radiation: Low Dose Radiation Therapy

Interventions

Low Dose Radiation Therapy RADIATION

Low dose whole brain radiotherapy delivered as an induction course of 10 fractions followed by 12 months of monthly maintenance LDRT in 10 fractions starting 2 months post-induction

Treatment Group

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥50 years at time of enrollment
• Externally confirmed diagnosis by a neurologist or geriatric psychiatrist (at Renaissance Institute, collaborating neurologist Dr. Sherif Makar, MD of Charis Neurology is available for diagnostic consultation) of one of the following: a. Alzheimer's disease (per NIA-AA 2011 or 2018 criteria) b. Frontotemporal dementia with documented inflammatory features c. Dementia with Lewy bodies with elevated inflammatory CSF markers d. Other neurodegenerative dementia with confirmed inflammatory component (elevated CSF IL-6, IL-1β, or TNF-α; or neuroimaging evidence of neuroinflammation)
• MoCA score 10-25 at baseline screening (moderate-to-mild cognitive impairment range)
• Karnofsky Performance Status (KPS) ≥60 or ECOG Performance Status ≤2
• Medically stable and capable of receiving radiation therapy as assessed by the treating radiation oncologist
• Reliable caregiver or informant able to accompany the patient to ≥80% of scheduled visits
• Written informed consent from patient (if decision-making capacity is preserved) and/or legally authorized representative (LAR); caregiver co-consent required
• Life expectancy ≥18 months in the opinion of the treating physician
• Ability and willingness to comply with monthly clinic visits for the 12-month maintenance period
• \--------------------------------------------------------------------------------------

You may not qualify if:

• Prior whole brain or partial brain radiotherapy of any dose at any time
• Active systemic malignancy requiring concurrent oncologic treatment
• Implanted device contraindicated with radiation therapy (pacemaker, cochlear implant, deep brain stimulator, or equivalent)
• Known active cerebral amyloid angiopathy-related inflammation (CAA-ri) or amyloid-related beta-angiitis (ABRA), whether confirmed by biopsy, CSF analysis, or neuroimaging features consistent with active leptomeningeal or parenchymal amyloid-related inflammation
• Active autoimmune encephalitis in acute phase (patients in stable chronic phase are eligible)
• Uncontrolled systemic infection or active sepsis at enrollment
• Severe psychiatric comorbidity (active psychosis, active suicidal ideation) impairing protocol compliance or safety assessment
• Concurrent enrollment in another interventional trial targeting cognitive decline or neuroinflammation
• Pregnancy or lactation; women of childbearing potential must use adequate contraception
• Inability to lie flat and still for radiation delivery (approximately 10-15 minutes per session)
• MoCA \<10 at baseline screening (severe dementia; insufficient cognitive range for endpoint assessment)

Sponsors & Collaborators

• Evan Thomas: lead

Study Sites (1)

Renaissance Institute of Precision Oncology & Radiosurgery

Winter Park, Florida, 32789, United States

RECRUITING

Related Publications (11)

• McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.

  PMID: 21514250 BACKGROUND

• Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018.

  PMID: 29653606 BACKGROUND

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Julayanont P, Brousseau M, Chertkow H, Phillips N, Nasreddine ZS. Montreal Cognitive Assessment Memory Index Score (MoCA-MIS) as a predictor of conversion from mild cognitive impairment to Alzheimer's disease. J Am Geriatr Soc. 2014 Apr;62(4):679-84. doi: 10.1111/jgs.12742. Epub 2014 Mar 17.

  PMID: 24635004 BACKGROUND

• Tang Q, Cheng Y. Enteral Nutrition: Based on the Combination of Nutrison Fibre and TPF-DM with A Marine Biological-Based Active Polysaccharide Preparation. Comput Math Methods Med. 2022 Jun 30;2022:6213716. doi: 10.1155/2022/6213716. eCollection 2022.

  PMID: 35813412 BACKGROUND

• Picard M. Blood mitochondrial DNA copy number: What are we counting? Mitochondrion. 2021 Sep;60:1-11. doi: 10.1016/j.mito.2021.06.010. Epub 2021 Jun 19.

  PMID: 34157430 BACKGROUND

• Wilson GD, Wilson TG, Hanna A, Fontanesi G, Kulchycki J, Buelow K, Pruetz BL, Michael DB, Chinnaiyan P, Maddens ME, Martinez AA, Fontanesi J. Low Dose Brain Irradiation Reduces Amyloid-beta and Tau in 3xTg-AD Mice. J Alzheimers Dis. 2020;75(1):15-21. doi: 10.3233/JAD-200030.

  PMID: 32280098 BACKGROUND

• Marples B, McGee M, Callan S, Bowen SE, Thibodeau BJ, Michael DB, Wilson GD, Maddens ME, Fontanesi J, Martinez AA. Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD). Radiother Oncol. 2016 Jan;118(1):43-51. doi: 10.1016/j.radonc.2015.10.019. Epub 2015 Nov 23.

  PMID: 26615717 BACKGROUND

• Kaul D, Ehret F, Roohani S, Jendrach M, Buthut M, Acker G, Anwar M, Zips D, Heppner F, Pruss H. Radiation Therapy in Alzheimer's Disease: A Systematic Review. Int J Radiat Oncol Biol Phys. 2024 May 1;119(1):23-41. doi: 10.1016/j.ijrobp.2023.11.044. Epub 2023 Nov 30.

  PMID: 38042449 BACKGROUND

• Kim A, Lee J, Moon H, Kim C, Yoo MY, Park WY, Kim WD, Seo YS. The effects of low-dose radiation therapy in patients with mild-to-moderate Alzheimer's dementia: an interim analysis of a pilot study. Radiat Oncol J. 2023 Jun;41(2):89-97. doi: 10.3857/roj.2023.00052. Epub 2023 Jun 26.

  PMID: 37403351 BACKGROUND

• Rogers CL, Lageman SK, Fontanesi J, Wilson GD, Boling PA, Bansal S, Karis JP, Sabbagh M, Mehta MP, Harris TJ. Low-Dose Whole Brain Radiation Therapy for Alzheimer's Dementia: Results From a Pilot Trial in Humans. Int J Radiat Oncol Biol Phys. 2023 Sep 1;117(1):87-95. doi: 10.1016/j.ijrobp.2023.03.044. Epub 2023 Mar 18.

  PMID: 36935024 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Evan Thomas, MD, PhD

  Renaissance Institute of Precision Oncology and Radiosurgery

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Pierson, BS

CONTACT

321-972-1102; jpierson@therenaissanceinstitute.org

Anita Stolaruk, RTT, MBA

CONTACT

321-972-1102; astolaruk@therenaissanceinstitute.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 13, 2026
• First Posted: July 9, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): May 21, 2029
• Study Completion (Estimated): May 21, 2029
• Last Updated: July 9, 2026

Record last verified: 2026-07

Locations

US (1)