Alzheimer DementiaPhase 1/2LDRT-MINDNCT07693140
Low-Dose Radiotherapy for Alzheimer's Disease
A Phase 1/2 study testing Low Dose Radiation Therapy in people with Alzheimer Dementia and Dementia, run by Evan Thomas at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Dementia, Dementia, Alzheimer Dementia (AD)
- What is being tested?
- Low Dose Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2026to 21 May 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
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Who cannot join
- 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)
- Brain MRI demonstrating any of the following: (a) more than 4 cerebral microhemorrhages on susceptibility-weighted imaging (SWI) or gradient echo (GRE) sequences; (b) more than 1 area of superficial cortical siderosis; (c) severe white matter disease (Fazekas grade 3); or (d) any macrohemorrhage or hemosiderin-stained lesion >10 mm. These thresholds are adapted from established AD trial imaging exclusion criteria to minimize enrollment of patients with advanced cerebrovascular disease or pre-existing hemorrhagic risk factors.
- 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)
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- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Renaissance Institute of Precision Oncology & Radiosurgery
Winter Park, Florida, 32789
Julia Pierson, BS, 321-972-1102, jpierson@therenaissanceinstitute.org
About this study
Official title: Low-Dose Radiotherapy for Alzheimer's Disease: A Phase I/II Open-Label Feasibility and Safety Study (LDRT-MIND Trial)
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
- Being tested
- Low Dose Radiation Therapy
- Keywords
- LDRT, Low-dose radiotherapy, Low-dose radiation therapy, Dementia, Alzheimer
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose Radiation TherapyRadiation
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Radiation: Low Dose Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
This secondary endpoint evaluates change in cognitive function measured by the Montreal Cognitive Assessment (MoCA), a 30-point scale on which higher scores indicate better cognition. The measure is the change in MoCA score from baseline to Month 12. The trajectory observed in the study cohort (N=50) is compared against a pooled published historical-control decline rate of 2.5 points per year (Tremont 2022; Julayanont 2014) using a Bayesian longitudinal mixed model for repeated measures with a robust meta-analytic-predictive historical-control prior. The prespecified hypothesis is that participants experience stabilization or a slower rate of MoCA decline than the historical reference. To mitigate practice effects, MoCA is administered on a rotating three-form schedule (Original, 7.1, 7.2), with rater identity and form version locked before prior scores become visible.
Measured: Baseline to Month 12, with MoCA assessed longitudinally across the maintenance period and at a standalone Month 12 cognitive endpoint visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2026
- Study start15 Jul 2026 (estimated)
- Primary completion21 May 2029 (estimated)
- Study completion21 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DementiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Evan Thomas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Evan Thomas, Renaissance Institute of Precision Oncology and Radiosurgery
- Investigators
- Evan Thomas, MD, PhD, Principal investigator, Renaissance Institute of Precision Oncology and Radiosurgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07693140
- Sponsor's protocol ID
- LDRT-MIND
- Acronym
- LDRT-MIND
- Status last verified
- Jul 2026
- First submitted
- 13 Jun 2026
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 21514250Jack 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.
PubMed 29653606Nasreddine 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.
PubMed 15817019Julayanont 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.
PubMed 24635004Tang 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.
PubMed 35813412Picard 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.
PubMed 34157430Wilson 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.
PubMed 32280098Marples 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.
PubMed 26615717Kaul 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.
PubMed 38042449Kim 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.
PubMed 37403351Rogers 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.
PubMed 36935024