The Safety and Efficacy of Sodium Pentaborate Pentahydrate in Patients with Mild to Moderate Alzheimer’s Disease: A Randomised, Double-Blind, Placebo-Controlled Phase 2 Trial

Determining the Safety and Efficacy of Sodium Pentaborate Pentahydrate in Patients with Mild to Moderate Alzheimer’s Disease

A randomised, double-blind, placebo-controlled phase 2 clinical trial with a sample size of 60 participants (30 per group), in which block randomization will be performed using the RAS software.

This double-blind clinical trial will be conducted at a clinic affiliated with Tabriz University of Medical Sciences. Both participants and study personnel, including researchers and those responsible for conducting the study, will remain unaware of treatment allocation until the end of the study. Participants will take a daily oral dose of sodium pentaborate pentahydrate or placebo after meals for 6 months, with study visits scheduled for screening, randomization (baseline), and follow-ups at 1, 2, 4, and 6 months.

Participants must be aged 55 to 85, diagnosed with mild to moderate Alzheimer's disease, with an MMSE score between 10 and 24, evidence of episodic memory impairment, and stable use of Alzheimer’s medications. Exclusion criteria include major neurological or psychiatric disorders, significant amyloid-related abnormalities on MRI, and recent use of experimental drugs.

Participants will be randomly assigned to two groups: one group will receive a placebo along with donepezil and 1000 mg of sodium pentaborate pentahydrate, while the other group will receive a placebo along with donepezil.

Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13)

Participants will be randomly assigned to two groups: the first group will receive sodium pentaborate pentahydrate (at a dose of 1000 mg) in combination with donepezil, while the second group will receive donepezil alongside a placebo. To allocate participants to the groups, a balanced block randomisation method at the individual level will be employed. The randomisation sequence will be generated by an independent individual, who is not involved in the study procedures, using RAS (Random Allocation Software). In this process, blocks of four with different arrangements of groups A and B will be used, and allocation will be carried out based on a random number table. The randomisation process in RAS involves the following steps: Defining the intervention group (A) and control group (B) in the software; Setting the block size (blocks of four); Generating all possible allocation combinations within each block (e.g., AABB, ABAB, ABBA, etc.); Randomly selecting blocks using a random number table; Concatenating the selected blocks to create the final allocation sequence. After evaluating the inclusion and exclusion criteria, eligible participants will be enrolled in the study sequentially and assigned to group A or B according to the generated sequence. For example, if the sequence begins with A, B, B, A, the first four participants who meet the criteria and enter the study will be allocated in this order. The allocation process will be concealed, and none of the researchers involved in the study will be aware of the allocation sequence or have the ability to manipulate participant assignment. Only the person responsible for generating the randomisation sequence will have access to it. To ensure blinding, each medication package will be labelled with a unique 10-digit random code. These codes will prevent both the participants and the study investigators from knowing whether the administered treatment is the active drug or the placebo.

Both participants and study personnel, including investigators and those responsible for study execution, will remain blinded to treatment allocation until the study is completed. Each active sodium pentaborate pentahydrate treatment group will have a matching placebo group with identical tablets to maintain blinding. Participants will take their assigned medication as a once-daily oral tablet after meals for six months. Study visits are scheduled for screening and randomisation (baseline), as well as at months 1, 2, 4, and 6.